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Radiation Effects Research Foundation News and Views
Hiroshima and Nagasaki, Japan

Volume 17, 2006

Table of Contents
From the Editors ............................................................................................................................................... 1
RERF NewsThe 32nd Scientific Council Meeting ........................................................................................................ 2
The 40th Board of Directors Meeting ....................................................................................................... 3
Staff News ..................................................................................................................................................... 5
Timofeef Award from the Russian Academy of Medical Sciences ......................................................... 5
Vice Chairman Dr. Waldren Receives Failla Award ................................................................................. 6
60th Anniversary of the A-bombings and 30th Anniversary of RERF’s Founding ............................... 6
Report on Conferences and Workshops
RERF Meeting: Radiation and Cardiovascular Disease, by Kazunori Kodama .................................... 7
Japan-U.S. Cooperative Cancer Research Seminar on Molecular Epidemiological
Characteristics of Lung and Colon Cancer Development among Atomic-bomb
Survivors, by Kei Nakachi ...................................................................................................................... 9
Science Articles
The Frequency of XPA Heterozygotes Bearing a Founder Mutation among
Individuals Who Resided in Hiroshima and Nagasaki, by Yuko Hirai et al. ................................... 13
The Introduction of Dosimetry System DS02 and Its Impact on Survivor
Doses and Related Risk Estimates, by Harry M. Cullings et al. ...................................................... 18
Human Interest Notes
Ties Strengthen Between Scientists at RERF and REAC/TS: An Update,by Gordon K. Livingston ....................................................................................................................... 22
Memory of a Firefighter of Chernobyl Accident, by Akio Awa ............................................................ 23
Mourning the Death of Dr. Robert W. Miller, by Kiyohiko Mabuchi .................................................. 24
In Memory of Dr. Shoichiro Fujita, by Fumiyoshi Kasagi .................................................................... 25
Facts and Figures ............................................................................................................................................ 27
Research Protocols and Publications
Research Protocols .................................................................................................................................... 28
Recent Publications ................................................................................................................................... 29
This newsletter is published by the Radiation Effects Research Foundation (formerly the Atomic
Bomb Casualty Commission), established in April 1975 as a private, nonprofit Japanese foundation.
It is supported by the government of Japan through its Ministry of Health, Labour and Welfare andthat of the United States through the National Academy of Sciences under contract with the
Department of Energy.
RERF conducts research and studies—for peaceful purposes—on the medical effects of radiation on humans with a view toward contributing to the maintenance of the health and welfare of
atomic-bomb survivors and to the enhancement of the health of all mankind.
Editor-in-Chief: Thomas Seed, Associate Chief of ResearchTechnical Editor: Yuko Ikawa, Public Relations & Publications Office
Editorial Policy
Contributions to Update receive editorial review only and do not receive scientific peer review.
The opinions expressed herein are those of the authors only and do not reflect RERF policies orpositions.
Contact: Mailing address: RERF Public Relations & Publications Office, 5-2 Hijiyama Park,
Minami-ku, Hiroshima 732-0815 Japan
Telephone: 81-82-261-3131; Facsimile: 81-82-263-7279
Internet: www.rerf.jp

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From the Editors, Letter to the Editor

Konnichi wa ……ii otenki desu ne!…
We do hope that you’ll find the contents of thislatest volume of the RERF Update both informativeand enjoyable. Despite our best effort to catch on
our reporting of RERF’s activities, we’re still a little
behind. Please bear with us; for in getting this issue
out, we believe that we will be able to start reportingon the most current of issues.
We thought that you’d appreciate seeing a picture of our new sign that has been recently installedin front of the main entrance to RERF. We find thisaddition, along with all the currently upgrading andrenovations to the physical plant to be quite symbolic of RERF’s current status……full of new starts,
new hopes, and plans for the future. The RERF
Update is no exception, for we are intent on innovating and improving the quality and the timelinessof our reporting of RERF activities. For example,
in terms of this volume of the RERF Update, we
believe that you’ll enjoy the science articles by Harry
Cullings, summarizing the major findings of new
DS02 report, and the report by Yuko Hirai on her
new, rather surprising observations of the relatively
high incidence of a genetic variant within the Life
Span Study (LLS) cohort that has been previously
linked to both radiosensitivity and susceptibility.
Further, the human interest story by Akio Awa on
RERF’s involvement with a Chernobyl firefighter
provides an insight into the global nature of RERF
activities, specifically as they relate to the long term
health effects of ionizing irradiation.
We are pleased to introduce below an e-mail let-ter from Mr. Kenji Joji, who retired in 1984 as chiefof the RERF Translation Office. He congratulates
us on the revival of RERF Update.
So please enjoy this volume, and of course feel
free to drop us a line and let us know your thoughts
on our reporting of RERF’s many activities.

Thank you very much for a copy of RERF Update Vol. 16, 2005, which I received in today’s mail.
I had been very concerned, for the last issue I received was Vol. 15, Spring 2004. I am looking forward to enjoying your latest issue, for RERF Update has been a historical documentation of RERF
since its inauguration in 1989 with Dr. J.W. Thiessen
being the first Editor-in-Chief and Ms. Beth Magura,
the Managing Editor.
As I have the entire series in a number of binders,
it would be greatly appreciated if you would kindly
arrange to place me on your mailing list as in the past.

I am also grateful to your RERF Newsletter* inbringing me up to date on the development and activities of RERF.

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Sincerely,

Thomas M Seed
Editor in Chief

Yuko Ikawa
Technical Editor

Sincerely yours,
Kenji Joji
September 30, 2006
* RERF intra-institutional publication distributed to former
and present RERF employees

RERF Update Volume 17, 2006

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RERF NewsThe 32nd Scientific Council meeting was heldon March 9–11, 2005 at the Hiroshima Laboratory,
and co-chaired by Drs. Yasuhito Sasaki and Gloria
M. Petersen, with the aim of reviewing RERF’s research programs. The meeting opened with RERF
Chairman Dr. Burton G. Bennett’s remarks, followedby an address from Mr. John S. Shaw, Assistant Secretary of the U.S. Department of Energy. Subsequently, there was a Chief of Research report, including a summary of the tentative RERF futureplans, and then the department chiefs made presentations summarizing the current status of departmental research programs. After that, departmental representatives reported on specific research projects;
the departments of Epidemiology and Clinical Studies made presentations on the first day and the departments of Genetics, Radiobiology/Molecular Epidemiology, Statistics, and Information Technology
on the second day. Upon completion of the departmental presentations, the Scientific Councilors held
a one-hour closed meeting with the RERF administration in order to discuss other issues. Then there
were informal department meetings attended by subgroups of the Scientific Councilors as well as therelevant research scientists, and over the course of
the meetings, problems were reviewed and departmental in-depth reports made.
The 32nd Scientific Council made nine generalrecommendations. The following are our responses
to the recommendations:
1. We very much appreciate the Scientific Council’s
consideration at what is a very crucial period for
RERF, as in addition to three senior staff retirements, the Vice Chairman (Dr. Taira) and one
Chief Scientist (Dr. Suzuki) left at the end of
March, and the Chairman (Dr. Bennett) as wellas the Chief of Research (Dr. Tahara) will step
down at the end of June. As recommended by
the Council, we will initiate strategic planningfor the near-term future of RERF to ensure thatscientific productivity will not be hampered.
2. We again appreciate the Scientific Council’s
strong recommendation that RERF’s sponsors
assemble an international Blue Ribbon Panel inconsideration of the past two years of internal
discussion on RERF’s long-term future. We sincerely hope that this Panel evaluates all options,considering the world heritage scientific resources that have been stored, and facilitatesplanning of RERF’s long-term future.
3. We agree whole-heartedly that RERF has an urgent need to recruit new scientists, particularly
members of an international staff. We will make
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4.

5.

6.

7.

8.

greater efforts to recruit such scientists throughadditional strategies proposed by the Council.
Regarding a review of existing policies of reimbursement for overseas and domestic scientificmeetings, we will consider changes in these policies to remove disincentives to attendance.
We very much appreciate the objective appraisalof the existing collaborations that have been established between RERF staff and outside scientists. We will further encourage RERF researchscientists to develop even more collaborations.
RERF has already discussed collaborative partnerships to foster visiting scientists and training
in the field of epidemiology and statistics between RERF and American or Japanese institutes. We will continue to discuss the possibilityof establishing both Japanese and American institutional partnerships as indicated in the response by the Department of Epidemiology.
Regarding data/biospecimen sharing, explicit
and transparent procedures for data/biospecimen
sharing have already been made by the Data
Sharing Committee, which was established inJuly of 2004. In order to promote collaborative
studies, the committee thoroughly discussed internal procedures to assure that RERF abides by
the law, to secure intellectual property rights, togive due consideration so that researchers involved do not feel that they are treated unfairly,
and to maintain security of the databases. We
are confident that a policy based on these procedures would encourage scientifically meritorious collaborations involving data/biospecimen
sharing with joint internal-external authorship.
Regarding publication of the DS02 standards
documentation, RERF has nearly completed the
publication of the DS02 report on behalf of the
U.S.-Japan Joint Working Group on the reassessment of the atomic-bomb dosimetry. Unfortunately, the Working Group has taken a long time
to finish the documentation of their work, asmany complex issues were involved. RERF has
had no control of this, and we have had to await
conclusion of these deliberations. All materials
received by RERF from the Working Group havebeen immediately and systematically formatted,
put into page set-up and passed on to the printer.
The work at RERF is thus at an advanced stage.
At present, almost all sections are completed,
and we need only finish the galley checking andrevision stage. The 1,000-page report should be
published by the end of summer 2005.
We concur that the international visibility of
RERF needs to be enhanced beyond the scope
RERF Update Volume 17, 2006

RERF Newsof the radiation research community. We will
make more efforts to publish in higher impact
journals, to improve the RERF website, and todevelop a public relations communications strategy.
9. We will make every effort to enhance communication, to stimulate more inter-departmental
collaborations, and to foster intellectual exchanges by creating research protocols (RPs)writing manuscripts, obtaining external researchfund, and holding informal inter-departmental
seminars as well as international workshops. In
addition, in order to maintain RERF’s scientificedge, we will consider the development of policies to encourage the review of productivity andaccountability of our scientific staff.
RERF Scientific Councilors
Dr. Yasuhito Sasaki, President, National Institute ofRadiological Sciences
Dr. Ohtsura Niwa, Professor, Radiation Biology
Center, Kyoto University
Dr. Toshitada Takahashi, Director, Aichi Cancer

The 40th meeting of the RERF Board of Directors was held for two days on June 22 and 23, 2005
at the National Academy of Sciences (NAS) in Washington, D.C. and attended by 28 individuals, including directors, supervisors, and observers. The Board
approved the appointment of the new chairman andother new directors, and the submission of a request
for establishment of a new Blue Ribbon Panel, a third
party group, charged with deliberating RERF’s future plans.
At the beginning of the meeting on day 1, RERF
Chairman Burton G. Bennett introduced the attendees. Mr. John S. Shaw, Assistant Secretary for Environment, Safety and Health, the U.S. Department ofEnergy (DOE), then said that the Scientific Council
in March had been a very productive meeting andthat he was looking forward to working with RERF’s
new chairman Toshiteru Okubo in RERF’s operations. Dr. Keiji Tanaka, Director-General, HealthService Bureau, Japanese Ministry of Health, Labourand Welfare, said that RERF is a unique research
institute cosponsored by the Japanese and U.S. governments, and that the Japanese government has ahigh opinion of RERF’s research and intends to support its research activities.
At the two-day meeting, all items for information and for deliberation and action were approved.
Some of the major items are mentioned below.
Comments made concerning the present personReturn to Table of Contents

3
Center Research Institute
Dr. Shinkan Tokudome, Professor, Health Promotion and Preventive Medicine, Nagoya City University Graduate School of Medical Sciences
Dr. Teruhiko Yoshida, Chief, Genetics Division,
National Cancer Center Research Institute
Dr. Gloria M. Petersen, Professor of Clinical Epidemiology, Mayo Medical School
Dr. Clarice Ring Weinberg, Chief, Biostatistics
Branch, Environmental Diseases and Medicine
Program, National Institute of Environmental
Health Sciences
Dr. Joel S. Bedford, Professor, Department of Radiological Health Sciences, Graduate Faculty of
Cellular and Molecular Biology, Colorado State
University
Dr. Roy E. Shore, Professor, Department of Environmental Medicine, New York University
School of Medicine
Dr. Theodore L. DeWeese, Professor and Chair,
Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine

nel status mentioned that RERF should probably review the possibility of increasing the retirement age
to 65 to enable productive researchers to pursue research and that the age limit should be applied to
NAS employees at RERF cautiously because there
is no age limit system in the U.S. The Board decided
that the RERF Executive Committee will further review these points together with a researcher performance evaluation system before these suggestions
are deliberated on at next year’s Board meeting.
The Board also deliberated on the report of theAnalysis Subcommittee of the Scientific and Ethics
Committees for the Health Effects Study of the Children of A-bomb Survivors, and agreed that the studyof second-generation A-bomb survivors is important,that it is necessary to fully investigate if there are
genetic effects, and that the study should be expanded
by increasing as much as possible the number of second-generation A-bomb survivors with high parental doses.
NAS explained the status of its efforts to recruit
employees to work at RERF. It has established a recruitment committee consisting of seven individuals and is presently conducting aggressive recruitment activities. It plans to recruit a total of six people:
two statisticians, two epidemiologists, a head of theStatistics Department, and an Associate Chief ofResearch.
Then the Board endorsed the establishment of a
RERF Update Volume 17, 2006

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RERF News
new Blue Ribbon Panel, as the RERF ScientificCouncil strongly recommended its establishment,
and because it will be beneficial for RERF to receive administrative and scientific opinions and useful as justification for the continued support fromthe two governments. Details such as the timing of
establishment and membership will be left up to thecompetent authorities.
In response, the Japanese government representatives commented that it will be useful for RERF’s
future to have its activities, including future plans,reevaluated by a third-party group. They also said
that RERF should start dealing with the relocation
issue by proposing an aggressive plan, including thetype of facilities RERF needs to conduct its researchin the future, if it wishes to relocate.
The DOE representatives commented in reply
that, whereas the mission of the previous Blue Ribbon Panel had been limited to scientific aspects, themission of the new panel seemed to be broader inscope as the panel would be required to deal with awider range of issues, which would probably be aheavy load for the body.
RERF Supervisor Dr. Tomio Hirohata said, as partof the FY2004 research activities report and audit
report, that the knowledge and wisdom of experts
should be gathered from an international perspective to consider RERF’s future because recently several researchers had resigned or moved to other institutions probably for reasons of insecurity about
their future at RERF. He also recommended that
RERF postpone the retirement of exceptional researchers till they reach the age of 65.
RERF Supervisor Mr. David Williams reported,as part of the FY2004 settlement of accounts and audit report, that although the RERF settlement of accounts had been reviewed by Pricewaterhouse Coopers (PWC), it was not an official audit because thefinancial documents did not include the unfunded portion of termination allowance liability or of the accrual
item of seasonable allowance payable in June 2005.
The Board of Directors then proceeded to the election of officers. Deliberation was made concerning
the appointment of successors to four Japanese directors (Drs. Toshiteru Okubo, Eiichi Tahara,
Hiromichi Matsudaira, and Takefumi Kondo) andthree U.S. directors (Burton G. Bennett, William J.
Schull, and John E. Burris). As a result, it was approved unanimously that Dr. Okubo be appointed aschairman, Dr. Charles A. Waldren as vice chairman,
Mr. Takanobu Teramoto as permanent director, Dr.
Yasuhito Sasaki as director, and Dr. Senjun Taira as
director, and that Dr. Schull be reappointed as permanent director and Dr. Burris as director. As successors to Scientific Councilors Drs. Yasuhito Sasaki,
Gloria M. Petersen, and Tadatoshi Takahashi, Dr.
Yoshiharu Yonekura (Director of Biomedical Imaging Research Center, University of Fukui), Dr.
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Marianne Berwick (Professor and Chief of the Division of Epidemiology, Department of Internal Medicine, University of New Mexico), and Dr. Katsushi
Tokunaga (Professor, Department of Human Genetics, Division of International Health, Graduate
School of Medicine, University of Tokyo) were appointed, respectively.
It was decided that the next Board meeting would
be held at Hiroshima RERF on June 21–23, 2006.
At the end of the meeting, Dr. Paul L. Ziemer, on
behalf of the Board, commended Dr. Bennett for
excellent leadership at RERF, and wished him wellin the future. With this, the Board completed discussion of all items on the agenda.
List of Participants
Permanent Directors:
Dr. Burton G. Bennett, Chairman
Dr. Toshiteru Okubo, Vice Chairman
Dr. Eiichi Tahara, Permanent Director and Chief ofResearch
Visiting Directors:
Mr. Masaaki Kuniyasu, Former Ambassador Extraordinary and Plenipotentiary to the Republicof Portugal
Dr. Hiromichi Matsudaira, Consultant, Radiation
Effects Association
Dr. Paul L. Ziemer, Professor Emeritus, Purdue
University
Dr. James D. Cox, Professor and Head, Division ofRadiation Oncology, University of Texas M.D.
Anderson Cancer Center
Dr. John E. Burris, President, Beloit College
Supervisors:
Dr. Tomio Hirohata, Professor Emeritus, Faculty of
Medicine, Kyushu University
Mr. David Williams, Senior Financial Advisor, National Academy of Sciences
Scientific Councilor:
Dr. Gloria M. Petersen, Professor of Clinical Epidemiology, Mayo Medical School
Representatives of Supporting Agencies:
Dr. Keiji Tanaka, Director-General, Health Service
Bureau, Ministry of Health, Labour and Welfare(MHLW)
Dr. Kazunari Asanuma, Deputy Director, General
Affairs Division, Health Service Bureau, MHLW
Mr. John S. Shaw, Assistant Secretary for Environment, Safety and Health, U.S. Department ofEnergy (DOE)
Mr. Steven Cary, Deputy Assistant Secretary for
Health, Office of Environment, Safety and
Health, DOE
RERF Update Volume 17, 2006

RERF News

5

Dr. Joseph F. Weiss, Japan Program Manager, Office of Health Studies, DOE
Mr. Kenji Kanasugi, Counselor, Embassy of Japan
Mr. Kazuhisa Takahashi, First Secretary, Embassyof Japan
Mr. Masahiro Mori, First Secretary, Embassy ofJapan
Ms. Kristina Midha, Global Affairs Officer, Officeof Japanese Affairs, Bureau of East Asian andPacific Affairs, U.S. Department of State
Ms. Nicole Nelson-Jean, Energy Attaché, Director,
U.S. Department of Energy Asia Office, Embassyof the United States of America in Japan
Dr. Warren R. Muir, Executive Director, Division on
Earth and Life Studies, National Research Council(NRC), National Academy of Sciences (NAS)
Dr. Kevin D. Crowley, Director, Board on Nuclear
and Radiation Studies, Division on Earth and Life
Studies, NRC, NAS
Dr. Evan B. Douple, Board on Nuclear and Radiation Studies, Division on Earth and Life Studies,
NRC, NAS
Ms. Catherine S. Berkley, Administrative Associate, Board on Nuclear and Radiation Studies, Division on Earth and Life Studies, NRC, NAS

In terms of RERF’s scientific staff, the “revolving door” continues to move. During the period from
April 2005 to March 2006, there have been three
new additions to the scientific staff, along with four
departures. The most prominent of staff was the appointment of Dr. Elichi Tahara as a “Senior Consulting Scientist,” and the invaluable role he has playedin establishing the “Study Group on A-Bomb Diseases” and associated cancer pathology network forongoing cancer studies here at RERF. [Note: Dr.
Tahara’s tenure as the Senior Consulting Scientist
was unfortunately relatively short-lived, and hasembarked on a course of full retirement.] Also on
the management side of the organization, Dr.
Thomas Seed joined the organization in December
2005 as the “Associate Chief of Research” for the
purpose of providing additional support for the departing Vice Chairman and Chief of Research, Dr.
Charles Waldren, and in turn, for the incoming newVice Chairman, Dr. Roy Shore. Finally, the Department of Genetics was fortunate to have rehired (viathe current “reemployment option” for retiring indi-viduals) a very excellent cytogeneticist and researchscientist, Dr. Mimako Nakano, who rejoined RERF
under the title of Adjunct Specialist.
During this period, RERF lost some outstanding
researchers who over the years made significant contributions to the RERF’s science. They are: Dr.
Catherine Sauvaget, a Research Scientist of Epidemiology Department, who worked on the epidemiology of “lifestyle issues” and who resigned on June30, 2005; and Dr. Shoichiro Fujita, Research Scientist and former Assistant Chief of Statistics Department, who suddenly died in April 2005, leaving an
emotional and scientific vacuum within the Statistics group. As Dr. John Cologne recently remarked
on Dr. Fujita’s scientific and statistical achievementsin the RERF Annual Report 2004 (page 21), “......
they were a large part of the success of RERF statistics program over the past several decades.”As mentioned above, RERF’s very distinguishedresearcher and administrator, Dr. Charles Waldren,
decided to vacate his post and to retire at the end of2005.

On October 25, 2005, the Russian Academy ofMedical Sciences (Chairman: Dr. Anatoly Tsyb) decided to present the Timofeef Award to the Radiation Effects Research Foundation for its significant
contribution to research into radiation effects on human health, and on November 14, an awarding ceremony was held in the Chairman’s Office at RERF’s
Hiroshima Laboratory. In the ceremony, Dr. Natalia
Seleva, who was training at RERF as a research fellow from the Medical Radiological Research Center of the Russian Academy of Medical Sciences,
presented a diploma and the commemorative medal
on behalf of Chairman Tsyb to RERF’s Chairman

Dr. Toshiteru Okubo.
The Timofeef Award was established in 1990 tocommemorate the 100th anniversary of the birth ofthe late Russian scientist N.W. Timofeef and to recognize his professional achievements, including his
advocating of the target theory of radiation damage
and Neo-Darwinism. The award since that time has
been presented to the researcher or researchers whose
achievements in radiation research are truly remarkable. In 1994, Dr. Itsuzo Shigematsu, former RERF
chairman, was the first Japanese recipient of theaward.

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RERF Secretariat:
Mr. Eiji Akimoto, Chief of Secretariat
Mr. Douglas C. Solvie, Assistant Chief of Secretariat
Dr. Charles A. Waldren, Chief Scientist

RERF Update Volume 17, 2006

RERF News6

Dr. Charles A. Waldren was selected as the recipient of the 2005 Failla Award, which is given by
the Radiation Research Society in the U.S. to an
outstanding researcher in recognition of significant
contributions to radiation research. An award ceremony and a commemorative lecture were held in
Denver, Colorado, in the United States, on October
16, 2005. We at RERF are very proud of Dr. Waldren
for his receipt of the award, and we would like toextend to him our sincerest congratulations. At theceremony venue, nearly 1,000 researchers gathered
as Dr. Robert Ullrich, president of the society, presented the award to Dr. Waldren. In his lecture after
the ceremony, Dr. Waldren introduced with a bit ofhumor some of his past achievements and the untold

stories behind them. Since Dr. Waldren maintains
close relationships with Japanese scientists including Dr. Akiko Ueno, a researcher with whom he hascollaborated for many years, and Dr. Masami
Watanabe, professor at Nagasaki University, he alsomentioned his collaborative research with these scientists and concluded his lecture by introducing his
research philosophy.
We sincerely congratulate Dr. Waldren on receiving the Failla Award. Although he retired from RERF
in December 2005, we will always appreciate thecontributions he made to RERF and wish him wellin all his future personal and scientific activities.
(Kazuo Neriishi)

A number of commemorative events relating to
the 60th anniversary of the atomic bombings were
held during the year of 2005 in Hiroshima andNagasaki. Although six decades have already passed
since the first atomic bombings in human history,
the A-bomb survivors still suffer from late effects ofradiation, and humankind still remains under the
threat of nuclear weapons. Amid continued aging of
the A-bomb survivors, who survived the horror of
the bombings after which it had been said that noplants or trees would grow for 70 years, serious discussion has taken place among related organizations
about how to convey this A-bombing experience tofuture generations. For RERF, that anniversary has
forced us to consider our future as a research organization in the face of the increasingly elderly population of A-bomb survivors, who continue to participate in our Life Span Study (LSS) and Adult HealthStudy (AHS), allowing us to obtain significant research results, and of projections of rapidly dwindling numbers in the near future of living A-bomb
survivors.
In addition to the 60th anniversary of the atomic
bombings, 2005 marked the 30th anniversary of
RERF’s founding. Thirty years had passed since theAtomic Bomb Casualty Commission (ABCC),
founded in 1947 by the U.S. government, was reorganized in April 1975 into the Radiation Effects Research Foundation, an organization jointly fundedby the governments of Japan and the U.S. As a commemoration of the anniversary, RERF held the 30th
Anniversary of the Establishment of the Radiation
Effects Research Foundation, and related lectures,at the Hiroshima Minami-Ward Community Cultural
Center on November 8, 2005, and at Wel City

Nagasaki, a public Kosei-Nenkin meeting hall, on
November 11. For the ceremonies, RERF invited themany A-bomb survivors who have cooperated over
the years in RERF’s health examinations. Many
former staff members of RERF were also in attendance, and other guests, including representatives of
the governments of the two nations, local individuals concerned, and A-bomb survivor representatives,offered their congratulations.
At the lecture meetings following the commemorative ceremonies, Dr. Ohtsura Niwa, professor at
the Kyoto University Radiation Biology Center, gave
a lecture titled “Contributions of RERF to Understanding Radiation Risk and Radiation Protection.”
Then, Dr. William J. Schull, RERF permanent director (Professor Emeritus and Ashbel Smith Professor of Academic Medicine, Human Genetics Center, School of Public Health, University of Texas,
Houston), spoke on the topic “The Radiation Effects
Research Foundation: After Thirty Years.” Both lectures were thoughtful and highly informative.
As part of the commemorative events, a ceremony
was held in Hiroshima involving the planting of aseedling from the offspring of the A-bombed aogiri(Chinese parasol tree), and an opening ceremony was
conducted in Nagasaki for a permanent exhibition
room introducing research activities to that facility’svisitors. After the ceremonies, a collection of recordsof the ceremony atmospheres and lectures, words ofencouragement from all sectors of society, andmemories of RERF from participants in our studies
in attendance at the ceremonies and from former
employees of RERF was published as RERF’s 30th
Anniversary Special Issue of the RERF Newsletter.

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RERF Update Volume 17, 2006

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Conference and Workshop Report

Kazunori Kodama, Chief Scientist andChief, Department of Epidemiology, Hiroshima
Recently, an increase in non-cancer disease (heartdisease, stroke, liver and other diseases) mortality
and incidence in RERF’s Life Span Study (LSS) and
Adult Health Study (AHS) cohorts was observed,
but no conclusion has yet to be drawn over whether
the increase is in effect attributable to A-bombradiation. Under such circumstances, a workshop
titled “RERF Meeting: Radiation and Cardiovascular Disease” was held on February 22–23, 2006, at
the Auditorium in Hiroshima. The meeting’s aim was
the determination of the future direction of RERF’s
research activities through in-depth discussions by
experts pertaining to such issues as “Is there sufficient epidemiological evidence proving the relationship between radiation exposure and cardiovasculardisease?” and “If radiation causes cardiovascular disease, what is the relevant mechanism?”Among participants from outside organizations
were Dr. Kiyohiko Mabuchi (Expert, Radiation Epidemiology Branch, U.S. National Cancer Institute:and former chief of RERF Epidemiology Department, Hiroshima), Dr. Fiona Stewart (Group Leader,
Experimental Therapy Division, Netherlands Cancer Institute), Dr. Steven E. Lipshultz (Professor andChairman of Pediatrics, University of Miami Schoolof Medicine), and Dr. Hirotsugu Ueshima (Professor, Department of Health Science, Shiga University of Medical Science), and all are internationallydistinguished researchers in this field of research. In
addition, three other specialists from Japan and the
U.S., and two postgraduate students from Kurume
University involved with the partnership program
participated. Also, with participation of directors andresearch scientists from RERF, enthusiastic discussions were conducted over two days.
The meeting revealed that: 1) even though theonset of cardiovascular disease due to high-doseradiation exposure is nearly unequivocally confirmed, we have insufficient epidemiological data
showing association between the disease and midand low-dose radiation exposure, as was the case in
the A-bomb radiation exposure, apart from the datain custody of RERF, and hence further accumulation and enlargement of such research data is requiredin order to comfirm the effects of radiation; 2) there
is no established theory for the mechanism of therelevant disease onset.
Among the future tasks for RERF pertaining to
the relevant study are: 1) enhancement of collectionof incidence data by way of enlargement of the AHS
cohort; 2) utilization of autopsy specimens; 3) introduction of echocardiography and carotid arteryechography to the AHS clinical examinations;4) measurements of insulin and inflammatory
cytokine levels as part of the clinical examinations;and 5) development of a new statistical analysis
methodology. Needless to say, continuation of theongoing follow-up studies is significant.
Even though more than 60 years have passed since
the dropping of the atomic bombs, the entire pictureof the health effects of A-bomb radiation has yet tobe elucidated, including the theme of this meeting,which was association between “Radiation and Cardiovascular Disease.” That means that there
remain numerous tasks to be addressed by RERF. I
also believe that everyone at RERF has the obligation and responsibility to work to elucidate all healtheffects of A-bomb radiation. I hope that all RERF
staff will make the necessary efforts to fulfill theirduties based on this common understanding.

— Program —February 22, 2006
“Opening Remarks”
Toshiteru Okubo (RERF)
Session 1: “Introduction”
Chairperson: Kazunori Kodama (RERF)“Evolution of studies on radiation and cardiovascular disease at ABCC-RERF”
Kazunori Kodama (RERF)“Goals of the workshop: Future research directions”
Roy E. Shore (RERF)
Participants of the meeting on radiation and cardiovascular disease held at the RERF Hiroshima Laboratory

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RERF Update Volume 17, 2006

8

Conference and Workshop Report
Session 2: “Epidemiology on radiation andcardiovascular disease”
Chairperson: Kiyohiko Mabuchi (NCI)“Radiation and non-cancer disease mortality in theLife Span Study”
Yukiko Shimizu (RERF)“Radiation effects on the incidence of cardiovascular disease and its risk factors (Adult Health Study)”
Michiko Yamada (RERF)“Radiation exposure and coronary atherosclerosis(Adult Health Study)”
Masazumi Akahoshi (RERF)
Session 3: “Epidemiology on radiation andcardiovascular disease (continued)”
Chairperson: Kiyohiko Mabuchi (NCI)“Late cardiovascular abnormalities following mediastinal irradiation in long-term survivors of childhood cancer”
Steven E. Lipshultz (University of Miami)“Review of epidemiological studies on radiation andcardiovascular disease”
Kiyohiko Mabuchi (NCI)
February 23, 2006
Session 4: “Possible mechanisms of radiation-induced atherosclerosis”
Chairperson: Gen Suzuki (NIPH)“Immune function, inflammatory markers andatomic bomb radiation”
Yoichiro Kusunoki (RERF)“Radiation-induced atherosclerosis in cancer survivors: Possible mechanisms and preventative intervention strategies”
Fiona Stewart (Netherlands Cancer Institute)“Metabolic syndrome as a risk factor of cardiovascular disease: Results of Tanno-Sobetsu Study”
Shigeyuki Saitoh (Sapporo Medical University)“Elevated risk of non-cancer disease can be a resultof adaptive response”
Nori Nakamura (RERF)
Session 5: “Discussion”
Chairperson: Roy E. Shore (RERF)“Closing remarks”
Roy E. Shore (RERF)

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List of Participants
Dr. Fiona Stewart, Group Leader, Experimental
Therapy Division, Netherlands Cancer Institute,
the Netherlands
Dr. Steven Edward Lipshultz, Professor and Chairman of Pediatrics, University of Miami Schoolof Medicine, USA
Dr. Kiyohiko Mabuchi, Expert, Radiation Epidemiology Branch, National Cancer Institute (NCI),
USA
Dr. Dale L. Preston, Principal Scientist, Hirosoft
International, USA
Dr. Hirotsugu Ueshima, Professor, Department of
Health Science, Shiga University of Medical Science
Dr. Gen Suzuki, Director, Department of Environmental Health, National Institute of Public Health(NIPH)
Dr. Shigeyuki Saitoh, Lecturer, 2nd Department ofInternal Medicine, Sapporo Medical University
Dr. Atsushi Kawaguchi, Postdoctoral Fellow, Biostatistics Center, Kurume University Graduate
School of Medicine
Dr. Yoshisuke Nonaka, Postdoctoral Fellow, Biostatistics Center, Kurume University Graduate
School of Medicine【RERF】
Dr. Toshiteru Okubo, Chairman
Dr. Roy E. Shore, Vice Chairman and Chief ofResearch
Mr. Takanobu Teramoto, Permanent Director
Dr. Nori Nakamura, Chief Scientist and Chief, Department of Genetics
Dr. Kazunori Kodama, Chief Scientist and Chief,
Department of Epidemiology, Hiroshima
Dr. Akihiko Suyama, Chief, Department of Epidemiology, Nagasaki
Dr. Saeko Fujiwara, Chief, Department of ClinicalStudies, Hiroshima
Dr. Masazumi Akahoshi, Chief, Department ofClinical Studies, Nagasaki
Dr. Kei Nakachi, Chief, Department of Radiobiology/Molecular Epidemiology
Dr. Hiroaki Katayama, Chief, Department of Information Technology
Dr. John B. Cologne, Acting Chief, Department of
Statistics
Dr. Yukiko Shimizu, Assistant Chief, Department of
Epidemiology, Hiroshima
Dr. Michiko Yamada, Assistant Chief, Departmentof Clinical Studies, Hiroshima
Dr. Yoichiro Kusunoki, Assistant Chief, Departmentof Radiobiology/Molecular Epidemiology

RERF Update Volume 17, 2006

Conference and Workshop Report

9

Kei Nakachi, Chief, Department ofRadiobiology/Molecular Epidemiology
This seminar was held on February 23–24, 2006,
in Bethesda, Maryland, as an activity of the JapanU.S. Cooperative Cancer Research Program for a
research project titled Molecular Epidemiological
Characteristics of Lung and Colon Cancer Development among Atomic-bomb Survivors (Japanese Principal Investigator, Kei Nakachi and U.S. Principal
Investigator, Curtis C. Harris; duration, April 1, 2004
– March 31, 2006), supported by both the Japan
Society for Promotion of Science and the U.S. National Cancer Institute (NCI). Mechanistic understanding of radiation-associated carcinogenesis is indispensable for the establishment of cancer prevention for those exposed to excess radiation, including
atomic-bomb survivors. This Japan-U.S. Cooperative Cancer Research Seminar was held to investigate future directions of molecular epidemiology
studies on radiation-associated cancer, on the basisof the data obtained thus far from studies in progress.
In the opening address, Dr. Curtis Harris (NCI, U.S.)
welcomed and thanked all the participants on behalfof the Japan-U.S. Cooperative Cancer Research
Seminar. Dr. Eiichi Tahara (RERF, Japan) also
thanked the participants and extended his gratitude
to Dr. Harris and the staff of his laboratory for organizing and hosting the seminar.
Overview of molecular epidemiology studies
among atomic-bomb survivors
Dr. Kazue Imai (RERF, Japan) gave an overview
on the occurrence of cancer and other diseases among
atomic-bomb survivors in relation to their past

Dr. Kei Nakachi making a presentation (center) and
Dr. Curtis Harris (right)

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exposure to atomic radiation. Using data collectedby the RERF Epidemiology Department, Dr. Imai
indicated that increased risk of cancer is to date themost important late effect of radiation exposure.
Following excess leukemia seen in the early years
after atomic-bomb exposure, significant excess riskof selected solid cancers also has been observed. Importantly, there is still excess risk for many solid cancers among radiation-exposed survivors even 60
years after the atomic bombings. However, themechanisms underlying these epidemiological findings remain unclear.
Based on these cancer data of atomic-bomb survivors, Dr. Kei Nakachi (RERF, Japan) overviewed
the molecular epidemiology studies currently being
carried out at RERF, emphasizing the need for amechanistic understanding of health effects ofradiation exposure, not only for disease prevention
among atomic-bomb survivors but also for establishing prevention strategies for radiation-associatedcancers and other diseases in general. The prevention of radiation-associated diseases, cancers in particular, is an important issue for many people, suchas patients undergoing radiation therapy, those occupationally or accidentally exposed to excess radiation, and even to people in the general population exposed to diagnostic X rays. In order to better
understand more about the mechanisms and prevention of radiation-related diseases, RERF Radiobiology/Molecular Epidemiology Department is currently using the three approaches of immunology,
immunogenome, and molecular oncology-based
studies. Evidence has recently accumulated supporting the idea that many lifestyle-associated diseases
such as coronary heart disease, diabetes mellitus, andeven cancer are associated with immunological alterations (e.g., chronic inflammatory responses anddisturbances of immunosurveillance systems) of thehost. This association has been investigated on thebasis of the altered immunity found among atomicbomb survivors, which can be observed even now,
60 years after the bombings. Immunology andimmunogenome studies include (i) T-cell repertoireand clonal expansions, (ii) T-cell functions and inflammatory response, and (iii) association between
cancer development and immune-related gene polymorphisms. Molecular oncology studies using thyroid, lung, and colorectal cancer tissue of atomicbomb survivors have recently begun at RERF with
RERF Update Volume 17, 2006

Conference and Workshop Report
the intent of discovering critical molecular events
within these cancers, but perhaps not in non-radiation-associated (sporadic) cancers. This study may
therefore underpin the molecular characteristics ofradiation-associated carcinogenesis.
Lung cancer – radiation-associated andsporadic
Dr. Michael Alavanja (NCI, U.S.) explained that
tobacco smoke and ionizing radiation might share acommon genotoxic mechanism, inducing oxidative
stress by transmitting or generating reactive oxygen
species (ROS). Dr. Alavanja hypothesized that glutathione-S-transferase M1 (GSTM1) null homozygotes would have decreased ability to neutralize
ROS, which might increase susceptibility to lungcancer. A case-only design was used with archival
tissue samples and radon concentration and secondhand smoke (SHS) exposure data among neversmokers from lung cancer cases pooled from threepreviously completed case-control studies. Radon
concentrations >120.62 Bq m–3 were associated witha >3-fold risk of lung adenocarcinoma for GSTM1
null homozygotes compared with GSTM1 carriers.
SHS exposure among never-smokers revealed a 2fold risk. Dr. Alavanja emphasized that genetic predisposition factors are probably more important in
low-dose carcinogenesis such as with SHS and radon exposures in home settings. Additionally, thesefindings supported the hypothesis that radon and SHS
promoted neoplasia through shared elements of acommon pathway.
To investigate the mechanisms of radiation-associated lung cancer, we need to understand the mechanisms of sporadic (non-radiation-associated) lungcancer among the general population. Dr. Leah
Mechanic (NCI, U.S.) examined association between
sporadic lung cancer and 14 TP53 polymorphisms,
including haplotype tagging and coding single nucleotide polymorphisms (SNPs), in an ongoing NCIMaryland Lung Cancer Case Control study, and subjects in a case-only study from the greater Baltimore
area were genotyped. Of these polymorphisms,
TP53_01 (Arg72Pro) and TP53_11 (T>G, IVS7+92)
were associated with increased risk of lung cancer
in African Americans. Individuals with combined
TP53_01 (Arg/Pro or Pro/Pro) and TP53_11 (T/Gor G/G) genotypes had elevated risk of lung cancer.
Moreover, individuals with Pro-T-A-G haplotypesof the combined TP53 polymorphisms TP53_01,
TP53_65, TP53_66 and TP53_16 had increased riskof lung cancer, compared to those with Arg-T-A-G
haplotypes. The TP53 Arg72Pro polymorphism wasshown to modulate p53 transcription-independent
apoptosis, through more effective mitochondrial localization. In this case-only study, TP53 haplotypes
were associated with increased TP53 somatic mutation frequency in lung cancer in Caucasians. The
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10
association between TP53 haplotypes and lung cancer will be further studied in radiation-associated lungcancer.
RERF epidemiology studies have indicated that
excess relative risk of lung cancer among atomicbomb survivors remained high even 60 years after
the atomic bombings. Dr. Masataka Taga (research
associate, NCI, U.S. and RERF, Japan) reported on
the current progress of a molecular oncology study
on lung cancer among atomic-bomb survivors, which
has been carried out in collaboration between the
Department of Radiobiology/Molecular Epidemiology, RERF and the Laboratory of Human Carcinogenesis, NCI, since 2004. P53 (exons 5–8), EGFR
(exons 18, 19 and 21), and K-ras (codons 12, 13 and61) gene mutations were examined in archival cancer and adjacent non-cancer tissue samples from 44
non-exposed patients and 28 exposed patients among
atomic-bomb survivors. The mutations were further
analyzed in relation to clinicopathological factors
including atomic-bomb radiation dose. Radiationexposed patients showed higher frequency of p53
mutation than that among non-exposed patients, although the difference was not statistically significant. Median radiation dose among lung cancer patients with p53 mutation of either G:C>T:A transversion or deletion was significantly higher than thatamong patients with other types of p53 mutations orthat among patients without p53 mutations. Of 15
exposed patients with lung adenocarcinoma or squamous cell carcinoma, two patients were found to have
p53 double mutations. On the other hand, EGFR
(or K-ras) mutations did not show association withradiation exposure. The results from this preliminary
analysis support the necessity of extended study withan increased number of patients, specifically those
exposed to high doses of radiation, along with analysis of other molecular events.
Dr. Naoko Sueoka (Saga Univ., Japan) reportedon EGFR mutations within sporadic lung cancer ofJapanese patients. EGFR mutations in lung cancer.
EGFR mutations were observed in 34 of 97 patients(35%): EGFR mutations were comprised of 1, 18,
and 15 mutations in exons 18, 19, and 21, respectively. Thirteen of the fifteen patients with exon 21
mutations were female non-smokers whose pathological type was adenocarcinoma with bronchioloalveolar carcinoma (BAC). The 18 patients withexon 19 mutations included eight male current orformer smokers. BAC was observed in eleven ofthese patients, which was less frequent than the caseof exon 21 mutations. These results of EGFR mutations in exon 21 and exon 19 suggest different
mutagenesis and carcinogenesis pathways involving
EGFR. Next, genetic host factors involved in occurrence of EGFR mutations were reported with specific reference to relationships between EGFR
mutations and the length of a CA-repeat in intron 1.
RERF Update Volume 17, 2006

Conference and Workshop ReportAllelic distribution of EGFR CA-repeat in lung cancer patients showed that 16 and 20 CA-repeat were
frequently observed. EGFR mutations were more
frequently observed in female non-smokers withfewer CA-repeat. In addition, dividing study patients
into three groups by number of CA-repeat (i.e., 16
or fewer, 17–19, 20 and more), EGFR mRNA levels
in normal adjacent tissue with 16 or fewer CArepeat were found to be higher than those of the othergroups.
Dr. Yun-Ling Zheng (Georgetown Univ., U.S.)
reported on relationships of γ -radiation-induced G2/
M arrest and DNA repair capability as assessed in
an ongoing case-control study on lung cancer, measured by quantifying bleomycin-induced chromosome breaks in cultured peripheral lymphocytes ofstudy subjects. The mean percentage of γ -radiation(1 Gy)-induced G2/M arrest was significantly lower
in cases than in both the general population groupand the hospital control group, and that, when
dichotomized at the 50th percentile value in combined control groups, a lower level of γ -radiationinduced G2/M arrest was associated with increased
risk of lung cancer among African-Americans. In
addition, mean number of bleomycin-induced breaks
per cell was significantly higher in cases comparedwith that in the control groups. These results imply
that both bleomycin-induced chromosome breaks
and less-efficient G2/M arrest induced by γ -radiation (1 Gy) are associated with increased risk of lungcancer among African-Americans, although theassociation was weaker in Caucasians.
Dr. Peter Shields (Georgetown Univ., U.S.)
overviewed several studies on cigarette smoking andgenetics, focusing on polymorphisms in the human
dopamine transporter (DAT1) gene and the dopamine receptor (DRD2) gene. A case (smokers)-control(nonsmokers) study revealed that smoking status was
greatly dependent on DRD2 genotype; a cohort ofhigh school students also showed that the risk of progressing from “puffing” to habitual smoking involved this genotype. A clinical trial using bupropion
to promote smoking cessation also showed greater
odds ratios (ORs) for the combined genotype of
DAT1 and DRD2 than that for use of bupropion vs. aplacebo. These findings suggest that future antismoking intervention will need to consider genetic
factors of individual smokers.
Colorectal, thyroid, and stomach cancers
found in atomic-bomb survivors
Epidemiological findings from the RERF cohort
study in atomic-bomb survivors have revealed thatcolon cancer showed significant risk elevation, while
rectum cancer did not. Microsatellite instability(MSI) reflects major genomic instability; MSI isassociated with proximal sites of the sporadic colon
carcinogenesis. Dr. Hidetaka Eguchi (RERF, Japan)
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11reported on the current progress being made in amolecular oncology study on colorectal cancer
among atomic-bomb survivors, focusing on MSI in
relation to atomic-radiation exposure. This study uses
archival cancer and adjacent non-cancer tissue
samples collected from 10 non-exposed and 27
exposed patients. MSI-positive colorectal cancer was
frequently observed at proximal sites in females, andthis was also the case in sporadic colorectal cancer.
Median radiation dose in MSI-positive colorectal
cancer patients was significantly higher than that in
MSI-negative patients; median age at the time ofatomic bombing or diagnosis in MSI-positive
patients was significantly lower than that in MSInegative patients. The latter finding seems to be inaccordance with the previous finding that colorectal
cancer among atomic-bomb survivors showed higher
excess relative risk among those exposed to atomicbomb radiation at younger ages. The results fromthis preliminary study suggest possible association
between radiation exposure and MSI status incolorectal cancer occurring among atomic-bomb
survivors. Further analyses with an increased number of patients will be needed, however.
Dr. Kiyohiro Hamatani (RERF, Japan) reported
on current progress in a study of thyroid papillarycancer (PTC) among atomic-bomb survivors, in viewof epidemiological data that this cancer was strongly
associated with radiation exposure. Archival cancer
and adjacent non-cancer tissue samples from 56
radiation-exposed (≥5 mGy) survivor patients and
29 non-exposed patients with PTC were analyzed,
in terms of the initial events in thyroid papillary carcinogenesis: RET rearrangements (RET/PTC) and
BRAFV600E mutation. Median radiation dose among
PTC patients with RET/PTC was significantly higher
than that among patients without RET/PTC. On theother hand, median radiation dose among the patientswith BRAFV600E mutation was significantly lower thanthat among patients without this mutation. Furthermore, median latency period (time period elapsed
from atomic bombing to diagnosis) and age at diagnosis in exposed patients with BRAFV600E mutation
were significantly longer and higher, respectively,
than those without the mutation; no association was
found between age at the time of atomic bombing
and BRAFV600E mutation. RET/PTC rearrangements
and BRAFV600E mutation were mutually exclusive.
These results suggest that initial choice of either RET/
PTC rearrangements or BRAF mutation may be influenced by atomic-radiation exposure, althougheach of them activates the RET/RAS/BRAF MAPK
signaling pathway.
Dr. Tomonori Hayashi (RERF, Japan) describedrecent findings on stomach cancer development
among atomic-bomb survivors, in terms of interaction between immunological host factors and radiation exposure. Immunological host protection is
RERF Update Volume 17, 2006

Conference and Workshop Reportconsidered to play an important role not only in thedevelopment of virus-related cancer, but also in carcinogenesis in general. On the other hand, exposure
to radiation affects the immune system of the host in
a dose-dependent manner. Case-control studies
within a sub-cohort of the RERF Adult Health Study
were conducted on the basis of immune-related gene
polymorphisms. One recent finding is an association between inflammation-related gene polymorphisms and stomach cancer development. Although
overall risk of stomach cancer significantly increased
with increased radiation dose, this risk was greatly
modulated in both non-exposed and radiationexposed survivors by IL-10 haplotypes, making possible the identification of people at high risk ofradiation-associated stomach cancer. This study also
demonstrated that plasma levels of IL-10 amongindividuals, which increased with past radiation doseand varied by IL-10 haplotype, indicated stomach
cancer risk of individual survivors as a promisingsurrogate marker of this cancer.
Mechanisms of radiation effects – in vitro
studiesDr. Simon Powell (Washington Univ., U.S.) focused on the role of p53 as a central regulator ofhomologous recombination (HR) and replication,
independent of its transactivation activity. By
employing a plasmid-based HR assay in p53-null
H1299 lung carcinoma cells, the HR-suppressing
properties of a panel of p53 mutants, which variedin ability to interact with human replication protein
A (RPA), were studied. Both wild-type p53 and atransactivation-deficient p53 mutant suppressed HR
and prevented RPA from binding to ssDNA both invitro and in vivo. Conversely, p53 mutations that specifically disrupt the RPA binding domain withoutcompromising the p53 transactivation function did
not affect HR or RPA binding to ssDNA. Suppression of HR was also lost with missense mutations in
the p53 core domain, which retained the ability tointeract with RPA, suggesting that additional binding interactions of p53 can also impact HR. After
substituting endogenous RPA2 either with an intact
myc-tagged analog (RPA2Wt), or with a phosphomimetic or a phosphorylation-deficient (RPA2D or
RPA2A) myc-tagged mutant, UV treatment led todissociation of the p53-RPA complex and an increaseof p53 transcriptional activity in the cells expressing RPA2Wt or RPA2D. RPA2A expression, on thecontrary, stabilized the p53-RPA complex and attenuated transcriptional activation of wild-type p53, although RPA2A failed to abolish transcriptional activation of p53 mutated within RPA binding domain.
These findings confirmed that the p53-RPA interac-

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12tion was critical for this regulation, and that the interaction was regulated by RPA phosphorylation;
RPA phosphorylation regulated p53 transcriptional
activity only in S-phase. Finally, the magnitude of
suppression of HR by p53 was greater for replication-associated HR, relative to DSB-induced HR.
These data suggest that p53 sequestering by RPA
regulates p53 transcriptional activity during S-phase,and that p53 binding to RPA regulates HR in S-phase.
The role of p53 in maintaining genome stability
might be significantly mediated by the p53-RPA
interaction in S-phase.
Dr. Tom Hei (Columbia Univ., U.S.) reported onrecent in vitro studies on low-dose radiation and the
bystander response. Observation of a bystander effect—i.e., induction of biological effects in cells notdirectly traversed by a charged particle but in close
proximity to cells that are —represents a paradigm
shift in understanding of radiation biology and target theory. This “bystander” effect was demonstrated
by chromatid damage within primary human bronchial epithelial cells not directly hit by traversing αparticles generated by a microbeam irradiation, butthat simply neighbor these cells that are directly hit.
Multiple pathways were involved in the bystander
phenomenon, and different cell types responded differently to bystander signaling. In confluent monolayers, gap junctional communication played acrucial role in mediating the bystander effect. Cells
without connexin gap junction protein showed no
bystander response, and p53 thus may not be essential. On the other hand, reactive oxygen and reactive
nitrogen species have been implicated as mediating
molecules in subconfluent cultures. A recent study
suggests that the cyclooxygenase-2 signaling cascade
plays an essential role in the bystander process. Treatment of bystander cells with NS-398, a COX-2 inhibitor, significantly reduced the bystander effectincluding HPRT mutation. Furthermore, upregulationof the extracellular signal-related kinases (ligands:
TNF-α, TGF-β, IGF, IL-1, and IL-8) and mitogenactivated protein kinases, specifically Erk and p38,
appear to represent important intercellular signaling
events of the bystander phenomenon. The implication of bystander observations is that the relevanttarget for various radiobiological endpoints is farlarger than the individual cell. This suggests a needto reconsider the validity of linear extrapolation in
calculating risk estimates for low-dose radiation
exposure.
All participants at this seminar agreed with thenecessity of promoting further collaboration between
Japan and U.S. researchers, to understand the effectsof radiation and the mechanisms of cancer induction for the benefit of all mankind.

RERF Update Volume 17, 2006

13

Science Articles: Frequency of XPA Heterozygotes

The Frequency of XPA Heterozygotes Bearing aFounder Mutation among Individuals
Who Resided in Hiroshima and Nagasaki
Yuko Hirai,1 Yoshiaki Kodama,1 Shin-ichi Moriwaki,2 Asao Noda,1 Harry M. Cullings,3Donald G. MacPhee,4 Kazunori Kodama,5 Kiyohiko Mabuchi,6 Kenneth H. Kraemer,7Charles E. Land,6 Nori Nakamura1
Departments of 1Genetics, 3Statistics, and 5Epidemiology (Hiroshima), and 4Research
Advisor, Radiation Effects Research Foundation; 2Department of Dermatology, Osaka
Medical College; 6Radiation Epidemiology Branch, 7Basic Research Laboratory, U.S.
National Cancer Institute
Introduction
Many cancer-prone autosomal recessive hereditary disorders are known to be caused by congenital
defects in DNA repair genes, but the frequency ofsuch disorders is quite low (on the order of several
cases per 100,000 individuals). However, the frequency of the heterozygotic condition is not at all
rare (in the order of one percent). Nevertheless it is
not well documented if the heterozygous carriers ofthese mutations are predisposed to cancer as well.
To address this issue, we sought to examine the frequency of heterozygotes bearing a specific mutationin the xeroderma pigmentosum group A (XPA) genein a small Japanese cohort.
XP is a rare autosomal recessive disorder in which
there is extremely high incidence of UV-related skincancers associated with an impaired ability to repair
UV-induced DNA damage.1 Eight genes, denoted as
XPA through XPG, plus a variant are known to be
responsible for the development of the XP disorder.
XPA to XPG proteins work in a coordinate manner
during the process of nucleotide excision repair(NER) of UV-induced DNA damage. In contrast,
patients with the XP variant are nearly normal in
NER but defective in post-replication repair due to amutation in the DNA polymerase η, a translesional
DNA polymerase.2
In Japan, the overall frequency of XP patients is
estimated as 1 per 40,000–100,000 newborns,3 whichappears to be more than 10 times higher than that inWestern countries.4 Interestingly, more than 50% ofJapanese XP patients belong to group A (XPA, genelocation: 9q22.3, OMIM 278700), clinically the most
severe form of both skin and neurological symptoms(Table 1) and this proportion is nearly twice that seen
in other countries.4,5 Further, about 80% of them havean identical G to C base-change mutation (a foundermutation).4 This founder mutation, at the 3′ splice
acceptor site of intron 3, results in no detectable protein production and creates a sensitive site within
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Table 1. Percentage of registered cases in the eight XP
complementation groups*
ComplementationgroupsJapanese
cases

Non-Japanese
cases

A
B
C
D
E
F
G
Variant

55.3
0
3.4
5.5
3.4
6.9
0.7
24.8

28.6
1.6
26.6
14.6
1.0
2.1
2.1
23.4

*From ref. 4.

the restriction enzyme AlwNI recognition sequence(denoted as the AlwNI mutation).6–8 Accordingly, it
is only necessary to examine one specific positionin the XPA gene in order to identify approximately
80% of XPA heterozygotes in Japanese people.
As a first step toward a molecular epidemiologic
assessment of cancer risks in XP heterozygotes, wedeveloped a simple PCR-RFLP (polymerase chain
reaction-restriction fragment length polymorphism)
method to identify XPA heterozygotes bearing thefounder mutation. We screened about 1,000 individuals who resided in Hiroshima or Nagasaki and collected direct information on the frequency of the XPA
heterozygotes, which should provide key information for determining the sample size of skin cancer
case in the subsequent study.9
Materials and Methods
Study subjects
We examined 1,884 Japanese donors, 904 from
Hiroshima and 980 from Nagasaki (only one siblingin each family was included in the present study).
These donors were the offspring of randomly selected
control subjects in a cytogenetic study aimed a clarifying the genetic effects of radiation in the progenyof atomic-bomb survivors. Control subjects were
RERF Update Volume 17, 2006

14

Science Articles: Frequency of XPA Heterozygotesborn to parents who were exposed to <10 mGy ofatomic-bomb radiation or born to those who were
not present in the city of Hiroshima or Nagasaki at
the time of the bombings.10

were repeated to confirm the character of the sample.
Finally, the amplified fragments analyzed thesequence to confirm the presence of the foundermutation.

Materials
Archived Giemsa stained blood lymphocytes,
collected about 20 to 30 years ago, were the sourceof the DNA for analysis. All the samples were coded
so that no links to the identity of the donors could bedetermined. Followed by removing mounting resin
from the slide by xylene, the Giemsa-stained lymphocytes were scraped off the slides by scalpels. The
cells were treated with proteinase K and the DNA
was concentrated by ethanol precipitation. The DNA
was suspended in H2O, and subjected to PCR-RFLP
analysis.

Statistical analysis
Confidence intervals for the prevalence of the XPA
founder mutation in the general population were calculated for the binomial distribution using Stata/SE
for Windows 9.1 (StataCorp LP, College Station,
Texas), which gives confidence intervals of the
Clopper-Pearson type.11
Results
Among the 1,884 lymphocyte samples that were
examined, the 61-bp-long DNA sequence was successfully amplified in 1,020 samples; 512 from
Hiroshima and 508 from Nagasaki. The overall success rate for PCR amplification was 54%. Amongthe 1,020 amplified samples, we found nine candidate mutation carriers where approximately half of
the amplified 61-bp fragments were cut into two
smaller fragments (25 bp and 36 bp) following AlwNI
digestion (Figure). Among these, four were from
Hiroshima and five from Nagasaki. All the AlwNI
digestion results were reproduced in a second assay
using the same DNA samples. In subsequent tests
using DNA from a second slide containing cells fromthe possible nine mutation carriers, seven DNA
samples were successfully amplified, and all of theseven samples produced the same results as thosewhich were obtained from the first slides. Furthermore, PCR products of two of these seven samples
were sequenced and confirmed as they carry the
AlwNI mutation in heterozygous conditions (results
not shown). However, two DNA samples out of thenine failed to yield PCR products using DNA fromsecond slides. It seems likely that these two cases
are also heterozygotes for the mutant allele since allof the other seven successful PCR samples gave rise

PCR and RFLP analysis
The DNA region that includes the founder mutation was amplified by PCR method. Our method
made use of two PCR primers (5′-TGGACTTAATCTGTTTTCA-3′ and 5′-CCTCTGTTTTGGTTATAAG-3′) to amplify sequences that include
intron 3 and exon 4 of the XPA gene. Aliquots of theamplified fragments (61 bp) were then digested with
AlwN1 or Hind III enzyme and subjected to polyacrylamide electrophoresis (12%) for separation. If
the founder mutation was present, the amplified 61bp DNA was further cleaved into two shorter fragments (25 bp and 36 bp long) with AlwN1. Hind III
treatment also cleaved the DNA into two shorter (butdifferently sized) fragments (23 bp and 38 bp), regardless of whether the mutation was present, andserved to confirm that the PCR-amplified fragments
were in fact derived from the relevant region of the
XPA gene (Figure). When a sample was suspected tocarry the mutation, PCR-RFLP was repeated using
the same DNA for confirmation. Subsequently, DNA
was extracted from a second slide and the same tests

(a)

(b)
A

AlwNI

B

- + -

C

+ - + -

D

E

+ -

A

+

HindIII
61
36

-

B

+ -

C

D

+ - + -

E

+ -

+
61
38

25
23
Figure. Representative electrophoresis patterns of PCR-RFLP with AlwNI (a) or HindIII (b) digestion. Lane A =normal control, B = positive control of XPA heterozygote carrying the founder mutation, C–E = test
samples of which C and D are normal, and E is a heterozygous carrier which is indicated by the two
shorter fragments (25 and 36 bp long) after AlwNI digestion (a).

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RERF Update Volume 17, 2006

15

Science Articles: Frequency of XPA Heterozygotes
to consistent results in the two independent sets of
PCR-RFLP tests.
The results indicate that the overall frequency of
XPA heterozygotes bearing the founder mutation in
the samples tested was 9/1,020 (0.88%, or 1 in 113)
with 95% confidence interval (CI) from 0.40% to
1.67%. There was no indication of differences
between Hiroshima and Nagasaki in the frequencyof the heterozygous individuals.
Discussion
This is the first molecular genetic, populationbased study focusing on XP heterozygotes. The
present study showed that the frequency of XPA heterozygotes bearing the founder mutation was 0.88%(1 in 113) among more than 1,000 donors from
Hiroshima and Nagasaki population. If this estimate
were representative of the general population, there
would be approximately 1 million carriers of the XPA
founder mutation in the 120 million people inJapan. And this value is somewhat higher than thefrequencies of XPA heterozygotes (0.47–0.74%) and
XPA heterozygotes bearing the founder mutation(0.41–0.65%) previously estimated by theoreticalextrapolation from the summarized findings of smallscale clinical investigations of XP patients.3 We
believe that our value, which was obtained byexamining the DNA from 1,020 individuals, is likely
to be the most realistic available to date.
Overall frequency of XP patients and heterozygotes
in JapanThe results reported here can be used to estimate
the overall frequency of XP patients and heterozygotes bearing a mutation in any one of the eight XP
genes as follows. If we assume that the population
frequency of normal allele as p and mutant allele
frequency as q (= 1 – p), the ratios of A = normal
individuals : B = XPA heterozygotes : C = XPA
homozygotes (patients) are expressed as p2 : 2pq : q2
(the Hardy-Weinberg equation). From the present
data, the frequency of heterozygotes is 2pq = 0.0088± 0.0030, so the frequency of XPA patients with the
AlwNI mutant allele is q2 = 1.96 ± 1.31 × 10–5 assuming random marriages (panmixia). Next, it waspreviously shown that 72 out of 92 XPA patients(78%) were homozygous for the founder mutation,
and almost all of the remaining cases were compound
heterozygotes; i.e., one allele contains the foundermutation and the other allele contains a different
mutation in the same gene.4 Thus, the frequency (1.96
× 10–5) was divided by 0.78 to estimate the frequencyof all XPA patients, which gave 2.51 ± 1.68 × 10–5
(Table 2, second line, column C). Using this value
and relative frequency of XP patients in each complementation group obtained from nearly 300 Japanese
XP patients (Table 2, column B), the frequency ofhomozygous patients was calculated for each groupfrom XPB to XP variant (Table 2, column C), whichgave the overall frequency of XP patients of
4.54 ± 3.04 × 10–5 (1 in 22,000) (Table 2, last line,
column C).
The frequency of heterozygous carriers of amutation in each XP gene was estimated as 2pq(Table 2, column D). The sum of 2pq of all the XP
groups gave 2.95 ± 1.04 × 10–2 (1 in 34 individuals,
Table 2, last line, column D). The frequency of heterozygotes for all of the XP disease genes comprising 1 out of 34 Japanese is impressively high.
In the past, several attempts were made to estimate the frequency of XP or XPA patients and heterozygotes in the Japanese population by indirect
methods. These are summarized in Table 3 along withthe present estimates. The past estimates used theWeinberg-Dahlberg equation, q = c (1 – k)/(16k –15c – ck) where c represents the proportion of firstcousin marriages in a general population and k represents the proportion in the parents of patients. It isclear that the present estimate of the frequency of
XPA heterozygotes (1 in 113) or XP heterozygotes(1 in 34), lies close to the highest value among thepast estimates.
It should be noted, however, that the present estimate of the frequency of heterozygotes of the XPA

Table 2. Estimated frequencies of heterozygotes bearing mutant XP genes
XP group

No. of XP
patients[A]

Fraction to thetotal XP patients(%) [B]

Frequency ofpatients(per 105) [C]Frequency ofheterozygotes(per 102) [D]

A
B
C
D
E
F
G
Variant

161
0
10
16
10
20
2
72

55.3
0
3.4
5.5
3.4
6.9
0.7
24.8

2.51 ± 1.68
00.16 ± 0.12
0.25 ± 0.18
0.16 ± 0.12
0.32 ± 0.22
0.03 ± 0.03
1.12 ± 0.77

1.00 ± 0.34
00.25 ± 0.09
0.32 ± 0.11
0.25 ± 0.09
0.35 ± 0.13
0.11 ± 0.05
0.67 ± 0.23

Total

291

100

4.54 ± 3.04
(1 in 22,000)

2.95 ± 1.04
(1 in 34)

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RERF Update Volume 17, 2006

16

Science Articles: Frequency of XPA Heterozygotes
Table 3. Summary of previous estimations on the frequency of XP (XPA) patientsand heterozygotes in Japanese
Genes

Frequency ofpatients (q2)

XPA
XPA
XP
XP
XP

1/42,000
1/570,000
1/23,000
1/18,000 to 31,000
1/100,000

founder mutation, 0.88% (9/1,020), includes a rather
wide 95% CI from 0.40% to 1.67%. If we assume atrue frequency equal to the lower bound, 0.4%, thefrequency of XPA patients is calculated as 0.51 ×
10–5 (1 in 195,000), nearly 5 times lower than theestimates using the mean value. Under these conditions, the overall frequency of XP patients would be
estimated to be 0.93 × 10–5. Consequently, the frequency of heterozygotes at any XP gene is estimatedas 1.32 × 10–2 (or 1 in 76 individuals), which is nearly
one half of the estimate using the mean value. Thisvalue closely related to past values.
We think there is no discrepancy between present
and past values from the view point that the registration of XP patients is unlikely to be complete (forexample, the symptom is mild and skin cancer isdeveloped over age of 40 in some complementationgroups). However, it is quite conceivable that themean frequency of heterozygotes observed in thisstudy could happen to be higher than the actual frequency in the general population and/or the
Hiroshima and Nagasaki population might not provide a good representation of the Japanese general
population.
Cancer risk in XP heterozygotes
The cancer risk of heterozygotes has only been
estimated in one large epidemiologic study of themembers of 31 XP families. Swift and Chase reported
30 out of 1,046 clinically normal adult blood relatives had skin cancer versus 11 out of 855 spousal
controls.12 This represents an odds ratio of 2.27 with
a 95% CI of 1.13 to 4.55. This result indicated thatthe frequency of skin cancer among blood relatives
was significantly higher than that in spouse controls.
Further, the skin cancers in blood relatives were concentrated in four families, and at least one of the families contained a mutation in the XPA gene, and therisk in the blood relatives in these four families wasnearly 15 times higher than among the spousal controls, while the risk in the relatives of the remaining
27 families did not show a statistically significant
increase when compared to risks in the spousal controls. The underlying cause for the skewed distribution of excess risks in the four XP families is notknown, but could be partly due to a difference,either in the defective genes (severe vs. mildly afReturn to Table of Contents

Frequency ofheterozygotes (2pq)

References

1/100
1/376
1/34
1/67 to 88
1/170

Present study
Maeda (ref. 13)
Present study
Neel (ref. 14)
Takebe (ref. 3)

fected phenotypes) and/or in the extent of the UV
exposure (i.e., the result of residing in the southern
vs. the northern states in the U.S.). This study was
published 25 years ago before any XP genes werecloned, so there was no laboratory test capable ofidentifying which of the blood relatives were heterozygotes.
Thus, skin cancer risk of XP heterozygotes seems
to be higher than that of normal individuals, although
how much higher is unclear.
In most other populations the frequency of XP ismuch lower than in the Japanese population, each of
the genes has many different disease causing mutations, and not all of these mutations have been identified. Any attempt to determine the frequency of XP
heterozygotes of any XP group in other populations
would require examination of a large number of possible sites in the relevant XP gene and as a result
would be virtually impossible. In this regard, theJapanese population is unusual because nearly one
half of the XP patients have mutations in the XPA
gene, and the vast majority of XPA patients bear theidentical founder mutation. Thus, a population-based
study on the influence of the XPA AlwNI mutationand cancer risks in XPA heterozygotes in the Japanese population is a feasible future study.
The frequency of XPA heterozygotes observed inthis study suggested the possibility that the risk ofskin cancer in XPA heterozygotes can be elucidated,
if we examine several hundreds of skin cancers. We
are preparing a research plan to evaluate the risk ofskin cancer in XPA heterozygotes.
Conclusion
We screened approximately 1,000 individuals
who resided in Hiroshima or Nagasaki to estimate
the frequency of heterozygotes bearing the foundermutation at xeroderma pigmentosum group A (XPA)
gene with PCR-RFLP method, as a preliminary study
for evaluation of excess risk of skin cancer among
the XPA heterozygotes. We identified nine such heterozygotes among 1,020 individuals screened(0.88%). This rate, if representative, implies that
there are about 1 million carriers of the XPA foundermutation in the Japanese population. Thus, investigation of their cancer risk may be warranted.

RERF Update Volume 17, 2006

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Science Articles: Frequency of XPA Heterozygotes

References
1.

Kraemer KH, Lee MM, Scotto J. DNA repair protects against cutaneous and internal neoplasia: evidence fromxeroderma pigmentosum. Carcinogenesis 5:511-4, 1984.

2. Cleaver JE. Cancer in xeroderma pigmentosum and related disorders of DNA repair. Nat Rev Cancer 5:564-73,
2005.
3. Takebe H, Nishigori C, Satoh Y. Genetics and skin cancer of xeroderma pigmentosum in Japan. Jpn J Cancer
Res 78:1135-43, 1987.
4. Moriwaki S, Kraemer KH. Xeroderma pigmentosum—bridging a gap between clinic and laboratory.
Photodermatol Photoimmunol Photomed 17:47-54, 2001.
5. Kraemer KH, Lee MM, Scotto J. Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalitiesin 830 published cases. Arch Dermatol 123:241-50, 1987.
6. Tanioka M, Budiyant A, Ueda T, Nagano T, Ichihashi M, Miyachi Y, Nishigori C. A novel XPA gene mutationand its functional analysis in a Japanese patient with xeroderma pigmentosum group A. J Invest Dermatol
125:244-6, 2005.
7. Satokata I, Tabnaka K, Miura N, Miyamoto I, Satoh Y, Kondo S, Okada Y. Characterization of a splicing
mutation in group A xeroderma pigmentosum. Proc Natl Acad Sci USA 87:9908-12, 1990.
8. Nishigori C, Moriwaki S, Takebe H, Tanaka T, Imamura S. Gene alterations and clinical characteristics ofxeroderma pigmentosum group A patients in Japan. Arch Dermatol 130:191-7, 1994.
9. Hirai Y, Kodama Y, Moriwaki S, Noda A, Cullings HM, MacPhee DG, Kodama K, Mabuchi K, Kraemer K,
Land CE, Nakamura N. Heterozygous individuals bearing a founder mutation in the XPA DNA repair genecomprise nearly 1% of the Japanese population. Mutat Res 601:171-8, 2006.
10. Awa AA, Honda T, Neriishi S, Sofuni T, Shimba H, Ohtaki K, Nakano M, Kodama Y, Ito M, Hamilton H.
Cytogenetic studies of the offspring of atomic bomb survivors. Obe G, Basler A, eds. Cytogenetics: Basic andApplied Aspects. pp 166-83, Spring-Bverlag, Berlin, 1987.
11.

Clopper CJ, Pearson SE. The use of confidence or fiducial limits illustrated in the case of the binomial. Biometrika
26:404-13, 1934.

12. Swift M, Chase C. Cancer in families with xeroderma pigmentosum. J Natl Cancer Inst 62:1415-21, 1979.
13. Maeda T, Sato K, Minami H, Taguchi H, Yoshikawa K. PCR-RFLP analysis as an aid to genetic counseling offamilies of Japanese patients with group A xeroderma pigmentosum. J Invest Dermatol 109:306-9, 1997.
14. Neel JV, Kodani M, Brewer R, Anderson RC. The incidence of consanguineous mating in Japan. Am J Hum
Genet 1:156-78, 1949.

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18

Science Articles: Impact of Dosimetry System DS02

The Introduction of Dosimetry System DS02
and Its Impact on Survivor Doses andRelated Risk Estimates
Harry M. Cullings, Sachiyo Funamoto, Sachiko Teranishi
Department of Statistics
In 2003, RERF implemented a new dosimetry
system, DS02. DS02 was developed primarily toaddress questions about the reliability of the neutron dose calculations of its predecessor, DS86: questions that arose from environmental measurements
related to neutrons from the atomic bombs. The
related issues were discussed in an earlier issue of
the RERF Update.1 In addition to complete new calculations of the fundamental quantities on which theestimates of survivor doses are based (radiation output of the bombs and transport of the radiation tolocations on the ground), the developers of DS02
provided a number of shielding modifications toaddress issues that arose in the years after the introduction of DS86. The new calculations of bomb output and radiation transport resulted in minor (orderof 10%) but uniform (same proportional change forall individual survivors at a given distance) changes
in the unshielded (“free-in-air”) doses that the dosimetry system calculates at ground level at all distances where survivors were located.1,2 In contrast,
the shielding modifications produced some fairly
large changes in estimated dose in some individuals, but these average out to minimal when averages
for the full Life Span Study (LSS) cohort are takenover reasonable-sized categories of DS86 dose or
distance, except for low-dose survivors in Nagasaki.
In this communication, we summarize briefly theeffects of DS02 on the doses calculated for survivors, and we discuss initial evaluations of the resulting impact on risk estimates.
The dose (D) calculated for any organ of any survivor can be factored into a free-in-air kerma (K)times a transmission factor (T), so that the organ dose
D changes in proportion to the changes in K and T.
DKTThat is, DS 02 ,n = DS 02 ,n × DS 02 ,n for neutrons
DDS 86 ,n
K DS 86 ,n TDS 86 ,n
DDS 02 ,g
K
T= DS 02 ,g × DS 02 ,g for gammas, and
DDS 86 ,g
K DS 86 ,g TDS 86 ,g
we can conveniently summarize changes in D aschanges in K and T. The T can be further factored
into two parts: one for the external (to the survivor’sbody) shielding provided by buildings and hills, andthe other for the shielding provided by the body itself, i.e., the shielding of deeper organs by overlying tissues, e.g., for neutrons, Tn = Texternal ,n × Tbody ,n .
andReturn to Table of Contents

Although the same relationships apply to both neutrons and gamma rays, the quantities D, K and T andtheir ratios are generally different, and the relationships for neutrons will be discussed separately anddistinctly from those for gamma rays.
Changes in K are described and explained in ref.
1: they are dominated by a change in the gamma
component, which is an increase of approximately
7% to 10%, for both Hiroshima and Nagasaki, at all
distances relevant to survivors. Changes in T, on theother hand, are a combined effect of changes in theenergy spectrum of the radiation reaching asurvivor’s location in the absence of shielding, andchanges in the way that shielding is calculated.
Changes in the energy spectrum can be summarized
quite succinctly: there was very little change in the
gamma-ray spectrum in either city, and a minor
reduction in overall neutron energy in both cities.2,3However, a few explanatory notes are in order,
especially in regard to the resulting changes in Texternal
and Tbody.
In regard to gamma rays, it should be noted that
there was a change in the spectrum of prompt primary gamma rays in the calculated output of both
bombs,2 i.e., those that were produced in the fission
chain reaction and “leaked” out of the bomb casingprior to the termination of fission, as well as anincrease in their total numbers. However, prompt primary gammas are a relatively minor part of the total
contributing to survivor dose, which is dominatedby prompt secondary and delayed gammas. Therefore, there is virtually no change in Texternal,g that isdue to the gamma-ray energy spectrum—the onlychanges in Texternal,g are due to the shielding modifications of DS02. And, because DS02 calculates the
body’s self-shielding by the same methods as DS86,
there is no substantial change in Tbody,g for any of theorgans.
As to neutrons, the decrease in overall energy
results in a small decrease in Texternal,n before the specific shielding modifications of DS02 are considered.
That is, for example, for house shielding that is notaffected by the shielding modifications of DS02, thechange in neutron energy causes Texternal,n to be a bit(~5%) less than that of DS86. This effect is attenuated in population averages by the fact that it does
not apply to persons who were outdoors. A slightly
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Science Articles: Impact of Dosimetry System DS02
larger effect, which applies uniformly to all survivors, is the effect of the change in neutron energy on
Tbody,n for deeper organs. For colon, for example,
Tbody,n in DS02 is about 6% to 9% less than in DS86.
The effect of DS02 shielding modifications on
Texternal for both neutrons and gamma rays can best
be understood by considering the nature of each
modification and the characteristics of the survivors
affected by it. The changes noted below are for
Texternal,g because gamma dose predominates; changes
in Texternal,n are generally similar.
• For persons in typical Japanese wooden houses,
the “frontal” shielding provided by adjacent buildings in the direction of the bomb was not considered in DS86 if the adjacent structure was moredistant from the survivor than twice its own height,
on the assumption that such more distant structures were at too low an angle to block out a significant fraction of the radiations coming from thebomb. However, it was determined later that theeffect of such more distant frontal shielding is not
negligible, particularly at longer distances from the
hypocenter where the bomb is at a low angle ofelevation above the horizon. DS02 calculates thisadditional shielding by using certain rules to divide the Monte Carlo results from the DS86 houseand tenement model clusters into three categories
based on the extent of such more distant frontal
shielding. During implementation of DS02, thefrontal shielding parameter for all affected survivors, 5,383 in Hiroshima and 2,166 in Nagasaki,
was re-coded by using geometric templates to apply the same classification rules to their shielding
history diagrams. Those in the new category withleast amount of “distant frontal shielding” had an
average increase of about 10% to 12% in their
Texternal,g, those in the middle category had a changeof only 1% to 2%, and those in the new category
with most such shielding had decreases of about
12% to 17%. These changes average out to almost
zero in the full group of affected survivors, whichis consistent with the fact that they essentially represent a rearrangement of the same Monte Carlo
results from the model house and tenement clusters that were used in DS86.
• A new “school” building model was developed for
persons in wooden schools and other similar large
wooden buildings, to replace the use in DS86 of
the model house and tenement clusters. In essence,buildings such as wooden schools were not being
properly represented by the model house and tenement clusters because they have larger rooms thanhouses and tenements; therefore the radiation passing through a school type building encounters
fewer wall and roof surfaces per unit distance, on
average, than in a wooden house or tenement. The
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19

new model resulted in an increase averaging 31%
for the Texternal of 639 persons in such buildings in
Hiroshima and 67 in Nagasaki.
• In 1989, the developers of DS86 provided RERF
with a method for calculating the shielding of survivors in two generic types of factory buildings in
Nagasaki, but these calculations modeled only thewalls and roof of the building and not any of its
interior features. For DS02, a large, three-dimensional forward-adjoint Monte Carlo calculation
was performed with a detailed model that included
some model workbenches with tools and metalparts situated on top of them, and two sets of calculations were performed for each of 40 modeled
worker positions, for a standing person and a person lying on the ground. In the implementation of
DS02, workers were considered to be standing
until the arrival of the blast wave, then lying down.
Under these assumptions, doses were reduced only
for positions within about 2 m behind a bench thatwas >30 m from the wall of the factory in the
direction of the bomb, and this reduction, which
affects only 97 of the 650 workers with position
data in factories to which the models apply, wasonly about –8% on average.
• In DS86, persons who were outside but near tobuildings had their shielding calculated by aso-called “globe” method. This was based on asimilar T65D method, for which a specially created variable had been evaluated for each survivor by using a spherical coordinate projector (alight bulb inside a clear sphere with markings) witha scale model of the survivor’s surroundings, todetermine the fraction of solid angle in specificdirections, relative to the direction to the bomb,that was blocked by buildings. In DS86, a weighted
sum of these increments of solid angle was calculated for each person and used to determine thesingle best Monte Carlo result to use from among
a number of such outdoor locations that were calculated in the model house and tenement clusters.
DS02 uses an average of the six outdoor Monte
Carlo results from the model house and tenement
clusters that have the nearest weighted solid angle
to the survivor whose shielding is being calculated.
This results in rather large changes for some of
the affected individuals, with a standard deviationof about 15% in Hiroshima and 19% in Nagasaki
for the % change in the Texternal,g. However, as withthe change in frontal shielding for those inside ofhouses, this essentially represents a rearrangementof Monte Carlo results that were already being usedin DS86, and the change averages to almost zerofor the affected 2,294 survivors in Hiroshima and593 in Nagasaki.

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Science Articles: Impact of Dosimetry System DS02
• In DS86, a method was devised to adapt T65D
globe calculations for small hills, but it was neverimplemented. In 1989, one of the developers ofDS86 provided RERF with a new, Monte Carlobased method for calculating terrain shielding
based on angles of elevation measured in five horizontal directions relative to the direction to the
hypocenter of the bomb: 0, ±45°, ±90°. This module was used for small hills in Nagasaki, which ismuch more hilly than Hiroshima. It was not clear
if this method could be used for the large hills
Hijiyama in Hiroshima and Konpirasan in
Nagasaki, but in developing DS02 it was established that this could be done. The implementation in conjunction with DS02 resulted in an average reduction of the Texternal,g of about –6% for 2,675
survivors in Hiroshima who were coded as being
affected by such “distal terrain” shielding, and –38% for 4,899 survivors in Nagasaki.
Thus, of all the shielding modifications, only thelast one listed, distal terrain shielding, produced asubstantial effect on relevant averages of doses calculated for the major RERF cohorts, predominantlyin Nagasaki because of the much larger size of
Konpirasan and the lower epicenter height of theNagasaki bomb, and only at longer distances beyond
that of Konpirasan. The frontal shielding and globe
modifications average out to very small differences
if taken over reasonably large subsets of survivors
classified in categories of distance or DS86 dose,the school model affects too few survivors to havemuch impact on averages based on the full cohort,and the new Nagasaki factory model produced littlechange in calculated shielding.
It should also be noted at this point that DS02
results regarding the Hiroshima hypocenter have noeffect on survivor distances or resulting doses. The

use of a geographical information system (GIS) in
developing DS02 resulted in a new alignment of the
war-era U.S. Army maps with more modern and detailed Japanese maps produced in 1979 for Hiroshima
and 1981 for Nagasaki. These newer maps are moreaccurate as well as more detailed, have coordinatesthat are verifiably correct in modern geographicalcoordinate systems, and generally conform to thestreet plans of present-day Hiroshima and Nagasaki.
The new map alignment allowed new estimates ofthe locations on the newer maps that correspond to
hypocenter estimates that had been produced completely in the context of the U.S. Army maps. Basedon the new map alignment, the location of theHiroshima hypocenter on the 1979 map was about
15 m west of two locations determined circa 1985
during the development of DS86, whereas the location of the Nagasaki hypocenter on the 1981 map
was less than 3 m from the location estimated circa
1985. Because the survivor distances currently used
at RERF are still based on the coordinates of the U.S.
Army maps, and the estimated locations of the hypocenters on the U.S. Army maps are not changedby the work done for DS02, there has been no change
in estimated survivor distances.
To sum up the effect of DS02 on survivor doses,
including the effect of changes in Tbody,n on the doses
to important deeper organs and tissues, the figure
addresses changes in colon dose. The curves in theDD
figure are plots of DS 02 ,n and DS 02 ,g for each
DDS 86 ,g
DDS 86 ,ncity, produced by grouping survivors on 50-m intervals of distance and smoothing the results. The curves
for gamma rays look very much like the changes inKg, which are shown in a similar plot in the previous
discussion in the RERF Update,1 because there areno substantial changes to Tg. The exception is thatthe effect of Konpirasan is seen in the downward

Figure. Ratio of DS02 colon dose to DS86 colon dose vs. distance.

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RERF Update Volume 17, 2006

Science Articles: Impact of Dosimetry System DS02
trend for Nagasaki at distances beyond about 2 km.
The curves for neutrons, however, are shifted downward by the effect of the lower neutron energy spectrum of DS02 on T external,n and Tbody,n. For similarreasons, at all distances in both cities, for all organs
and tissues, the ratio of neutron dose to gamma doseDD
is less in DS02 than in DS86: DS 02 ,n < DS 86 ,n . In
DDS 02 ,g
DDS 86 ,gNagasaki this difference is quite pronounced, butDof negligible consequence because DS 86 ,n was
DDS 86 ,galready very small in Nagasaki.
Shortly after the implementation of DS02, its effect on risk estimates was initially evaluated for solidcancer and leukemia mortality in the LSS.4 The estimates of excess relative risk (ERR) per gray, modeled as linear for solid cancer and linear-quadratic
for leukemia, both decreased by about 8% due to theincreases in estimated gamma dose. There were noother changes attributable to the DS02 vs. DS86
dosimetry, including no substantial changes in agetime patterns and sex differences. This does not establish, of course, that changes would necessarily
be negligible for other RERF cohorts or subcohorts,
particularly in studies utilizing smaller groups of21

survivors in which individual dose changes due tothe DS02 shielding modifications may not be subject to as much averaging as in the full LSS.
Contemporaneously with the implementation of
DS02, the roster of survivors with calculated doses
was considerably expanded, as detailed in ref. 3. As
noted in that summary, research and related work
will continue on a number of areas of implementation, including the methods used to deal with dose
error, the use of the GIS with maps, aerial photographs and survivor shielding history drawings to
improve estimates of survivor location and possibly
some aspects of shielding, and particular attention
to the case of the Nagasaki factory workers. Much
greater detail on all of the matters related to DS86
and DS02 is given in the related reports, which areavailable online at RERF’s website under “Publications.” For example, Chapter 11A of the DS02
report2 explains why the anticipated changes in dose
estimates for the Nagasaki factory workers were notrealized, and suggests areas for further research. In
addition, the U.S. National Cancer Institute has graciously made the extensive review of dosimetry inref. 3 available to the public free of charge on theirwebsite at http://dceg.cancer.gov/radia/res35.html.

References
1.

Cullings HM, Fujita S. The way to DS02: Resolving the neutron discrepancy. RERF Update 14(1):17-23, 2003.

2.

Young RW, Kerr GD, eds. Reassessment of the Atomic Bomb Radiation Dosimetry for Hiroshima and Nagasaki—
Dosimetry System 2002. Radiation Effects Research Foundation, Hiroshima, 2005.

3.

Cullings HM, Fujita S, Funamoto S, Grant EJ, Kerr GD, Preston DL. Dose estimation for the atomic bomb
survivor studies: Its evolution and present status. Radiat Res 166:219-54, 2006.

4.

Preston DL, Pierce DA, Shimizu Y, Cullings HM, Fujita S, Funamoto S, Kodama K. Effect of recent changes inatomic bomb survivor dosimetry on cancer morality risk estimates. Radiat Res 163:377-89, 2004.

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RERF Update Volume 17, 2006

22

Human Interest Notes

Ties Strengthen Between Scientists at
RERF and REAC/TS: An Update
Gordon K. Livingston
Radiation Emergency AssistanceCenter/Training Site (REAC/TS)
The 2nd International Conference on Biodosimetry and the 7th International Symposium on
EPR Dosimetry and Applications were held on July
10–13, 2006, at the Uniformed Services Universityof the Health Sciences in Bethesda, Maryland. This
meeting provided an ideal venue for scientists affiliated with RERF and REAC/TS to present a joint
paper entitled, “An Automated Method to Quantify
Radiation Damage in Human Blood Cells” authoredby Drs. Gordon Livingston and Mark Jenkins of
REAC/TS and Dr. Akio Awa, cytogenetic consultant to RERF. A fruitful collaboration between Drs.
Awa, Nori Nakamura, and myself had already developed via e-mail over the previous two years but
it was not until the biodosimetry conference that theinvestigators finally had an opportunity to meet eachother in person (see the photo below).

chromosome preparations obtained from former U.S.
plutonium workers on whom FISH-based studies had
already been completed. Surplus slides were available for further evaluation for 15 controls and 15
exposed individuals using conventional Giemsa
staining and automated karyotype analysis. The useof the 7–8 year old unstained slides presented aunique opportunity to validate and confirm the earlier RERF studies and to compare data from the Abomb survivors whose exposures were acute external doses with former plutonium workers whose
exposures were chronic and mainly the result of internal deposition of plutonium. Furthermore, it wasworthwhile to compare the data from the FISH andconventional Giemsa staining methods to see
whether the frequency of total translocations was
similar using different methods of analysis. Results
showed good agreement for both the control andexposed groups. The data obtained from the former
plutonium workers confirmed the earlier work published by scientists at the RERF on atomic bomb
survivors who had demonstrated the value of solid
Giemsa staining in detecting stable chromosome
aberrations (see the Figure).

(From left) Dr. Akio Awa from RERF, Drs. Gordon
Livingston and Patrick Lowry from REAC/TS, and Dr.
Yoshiaki Kodama from RERF. (Not pictured from
REAC/TS are Drs. Al Wiley and Mark Jenkins—photographer)

As described in the previous issue of the RERF
Update, a fruitful collaboration developed as a result of two publications, one authored by Dr. Mimako
Nakano and co-workers in the Cytogenetics Laboratory at the RERF that compared cytogenetic data
based on solid Giemsa staining with FISH-based
staining for 230 A-bomb survivors and the secondby Dr. Awa, entitled “Biodosimetry of Human Exposure to Radiation: A Manual for Detecting Stable
Chromosome Aberrations by the Conventional Giemsa Staining Method” published on the RERF
website. These two RERF publications combined
to provide the stimulus for me to further evaluate
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Figure. Karyotype showing chromosome aberrations:
Inversion in chromosome (1)/Translocations in chromosomes (4, 9) and (15, 15).

The follow-up cytogenetic study of the plutonium
workers was ultimately funded by the Departmentof Energy (DOE) through the National Institute for
Occupational Safety and Health (NIOSH), and the
DOE-EH (Office of Environment and Health) continues to support the REAC/TS Cytogenetic
Biodosimetry Laboratory (CBL) in Oak Ridge, Tennessee.
RERF Update Volume 17, 2006

23

Human Interest Notes
In addition to the attendance and collaborationon the presentation at the Biodosimetry Conferencein Bethesda, Drs. Kodama and Awa traveled to Oak
Ridge to serve on the REAC/TS CBL Scientific
Advisory Board (SAB). The SAB will provide technical advice and guidance on the re-establishmentof a cytogenetics laboratory at the Oak Ridge Institute for Science and Education (ORISE)/REAC/TS.
The SAB will help to ensure that the REAC/TS
Cytogenetic Biodosimetry Laboratory will be reestablished in a timely manner and will produce thehighest quality analyses.
While in Oak Ridge for the day, the international
members of the SAB and some of the REAC/TS staff
took an opportunity to visit the International Friendship Bell that is the first monument between a U.S.
Manhattan Project city and Japan and serves as an
expression of hope for everlasting peace.

(From left) Drs. Daniela Stricklin (FOI-Sweden), Joe
Weiss (U.S. DOE-EH), David Lloyd (HPA-England),Patrick Lowry, Gordon Livingston (REAC/TS-USA),
Akio Awa, and Yoshiaki Kodama (RERF-Japan) visited the International Friendship Bell in Oak Ridge.
(Not pictured is Dr. Mark Jenkins [REAC/TS]—photographer.)

Memory of a Firefighter of Chernobyl Accident
Akio Awa, former Associate Chief of Research
For me, the year of 1989 was a busy one, and one
to be remembered. Early in 1989, I received an invitation letter as a speaker of the plenary session fromthe organizing committee of the International Conference on “Chromosome Aberrations—Basic andApplied,” to be held in Essen, West Germany, 5–7
October 1989. That was a month before two Germany countries were reunited. Soon after I accepted
this invitation, I was asked by Professor Kenjiro
Yokoro to give a talk on the genetic effect of atomic
radiation of the offspring of A-bomb survivors at the
symposium of the International Physicians for thePrevention of Nuclear War (IPPNW) to be held in
Hiroshima and Nagasaki on October 5–12, 1989. Dr.
Yokoro then was a professor in the Pathology
Department of the Research Institute of Radiation
Biology and Medicine at Hiroshima University, andconcurrently the secretary-general of the Japan
IPPNW branch office. To my surprise and perplexity, dates of two international meetings overlapped
perfectly, and about as far separated on the globe as
one could get, i.e., the one meeting in Europe andthe other in Japan. Nevertheless, I found a way toattend both the meetings, provided a neat and tightschedule was followed. I ended up giving a one-hourtalk at Essen in the evening of October 5, and immediately left the next day for Narita, Japan, via stopovers in Düsseldorf and Frankfurt. Although thetravel schedule was tight and rather difficult, it was
the only way to get back to Hiroshima to make
IPPNW meeting and to give my talk on schedule.
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Somehow I managed it, but it felt as though I waswalking on a tight-rope.
The IPPNW Colloquium opened in the morningof October 8 at the International Conference Center
Hiroshima in Peace Memorial Park. The majority ofthe speakers at the colloquium were RERF scientists, and all of the papers were well received bythose in attendance. After my session, Dr. Itsuzo
Shigematsu, a former RERF chairman, told me that
one of the Chernobyl firefighters was attending themeeting and would be visiting RERF on October 10
and would be receiving various clinical and laboratory examinations. The firefighter’s name was
Major Leonid Petrovich Telyatnikov, the commanderof the Chernobyl Fire Department at the time of theaccident, April 26, 1986. He was invited by the conference organizers to come to Hiroshima and to givea talk about his own experience in fighting the fires
associated with the Chernobyl reactor accident. Dueto my getting to conference a bit late, I didn’t have achance to listen to his lecture, but I was told that his
talk was highly informative and deeply moving.
Mr. Telyatnikov visited RERF in the morning of
October 10. He was quiet and kept smiling all thetime. He was 38 years old at the time of examination, being 3 and-a-half years after the Chernobyl
accident. When we met he looked apparently healthy.
When I saw his dark hair, it was hard to imagine his
hairless head at the time he was out of the hospital
after emergency treatment in 1986. In those days, I
had a chance to read many books regarding the
RERF Update Volume 17, 2006

24

Human Interest Notes
Chernobyl disaster in which many photographs of
his with loss of hair were documented.
His blood was drawn by Dr. Kazuo Neriishi at
the RERF clinical facilities (for detail, see RERF
Update, Volume 1, Issue 4, Winter 1989–90, pages
1–2). The blood was brought to Cytogenetics Laboratory where tissue culture and preparations of
microscopic slides for chromosome aberration analysis would have been conducted. We employed allavailable cytogenetic techniques, such as conventional stain, trypsin-Giemsa banding stain (GTG),
Fluorescence plus Giemsa (FPG) stain with BrdU.
In those days, however, FISH (Fluorescence in situ
hybridization) stain technique was not available at
RERF.
The purpose of chromosomes aberration study
was to estimate radiation dose received by him bymeans of cytogenetic biodosimetry analysis. The
chromosome
analysis was
performed successfully. In accordance with
our anticipation,
we could detecta large numberof complicatedstructural rearrangements ofchromosomes in
his peripheral
blood lymphocytes. This indicated that hemust have rePortrait of Mr. Leonid Petrovich ceived as highas fatal radiation
Telyatnikov (date of photography
unknown), by courtesy of Mrs. dose during his
Larisa Ivanovna Telyatnikova.
fire-fighting ac-

tivity. We could confirm that our suspicion proved
to be true. After analysis and calibration of data, hisradiation dose was estimated to be in the range of 4–
5 Gy that corresponds to the LD50 dose in man. Subsequently, a summary form of the results was submitted to the Chairman’s office.
In December of 2004, I learned through the news
media that Mr. Leonid Telyatnikov passed away at
the age of 53 due to cancer of the jaw. The year 2006
is the 20 years anniversary of the Chernobyl nuclear
power plant accident. This reminded me two important things which I completely ignored for years. One
was that I did not report of our findings to our client,
Mr. Telyatnikov, and the other was that the data had
been left unpublished. For the former, thanks to thestrong support of the staff of Kyodo Press in Japanand in Moscow, the report of our data was delivered
to his bereaved family members in Kiev, Ukraine,
together with my apology for not sending any reportto them. The apology was accepted by the family.
I started to re-visit the cytogenetic data, whichhave been kept as an official document of the
Department of Genetics. The data seemed to include
some important findings. I personally consulted thismatter with my old friend who is known as an expert in this research area. He gave me advice that thedata be published promptly, and that it is not yet toolate to do so. A manuscript is being in progress andready for receiving criticisms and comments fromthe RERF Scientific Report Review Committee forapproval of publication.
Before closing this personal account of recollection, I wish to thank all of the research and technicalstaff of the Cytogenetics Laboratory, as shown in
the following. Professional staff: Dr. Yoshiaki
Kodama, Dr. Kazuo Ohtaki, and Dr. Mimako
Nakano. Technical staff: Ms. Sumie Murata, Mr.
Masashi Hiramoto, Ms. Kaori Muramoto, Ms. Miwa
Miura, and Mr. Junso Takayama (photographer).

Mourning the Death of Dr. Robert W. Miller
Kiyohiko Mabuchi
Radiation Epidemiology Branch
U.S. National Cancer Institute
Dr. Robert W. Miller, who greatly contributed tothe epidemiological research of A-bomb survivors
at ABCC and RERF, passed away at the end of February in 2006. As a pediatrician, Dr. Miller was interested in radiation biology and genetics, and madeimportant and unique contributions to the study of
association between congenital deformities and cancer and to many other fields of study. Dr. Miller came
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to Hiroshima in 1953 and was assigned to the position of chief of ABCC’s pediatrics department. He
produced important study results in terms of microcephaly and mental retardation among children exposed in utero and childhood leukemia, although hisachievements failed to attract any attention at thattime. In those days, the framework of epidemiological research of A-bomb survivors, with the Life Span
RERF Update Volume 17, 2006

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Human Interest Notes
Study playing a key role, was established under theFrancis Committee. During this most important transitional period in ABCC-RERF’s history, Dr. Miller
made notable contributions as a pioneer in epidemiological research at RERF. After returning to theUnited States, he was appointed the first chief of theepidemiology department at the U.S. National Cancer Institute (NCI). Stressing the importance of epidemiological research on A-bomb survivors, Dr.
Miller consistently supported RERF’s study program
through the National Academy of Sciences (NAS)and the RERF Scientific Council. Dr. Miller also initiated the tissue registries in Hiroshima and Nagasaki
through NCI. Furthermore, under the U.S.-Japan
joint study group he organized, Dr. Miller promotedcooperation with many Japanese researchers outside
RERF. Based on his own experience, Dr. Miller
emphasized that keen observation at a patient’s bedside would lead to the identification of the cause of
his/her disease. He did not like to follow the crowd,
and had unique viewpoints in every respect. On oneof its cover pages, the New Yorker once carried aphotograph of several birds on an electric wire looking in one direction, with only one bird looking theDr. Robert W. Miller in 1979

other way. Dr. Miller considered himself to be likethat single bird. Dr. Miller’s memoirs of ABCCRERF consisting of four parts were published in the
RERF Update from 1993 through 1998. The memoirs show his intellectual energy, keen powers ofobservation, and sense of humor. Mrs. Holly Miller
is Japanese and used to be a nurse at RERF.

In Memory of Dr. Shoichiro Fujita
Fumiyoshi Kasagi, Assistant Chief
Department of Epidemiology, Hiroshima
It was April 3, 2005, when I received the sad newsof the sudden passing of Dr. Fujita. When I hurried
to his home and saw him lying in peace on his bedding, I could not stop crying. His personality
appealed to many people. He had his own clear standards of right and wrong, and he always dealt withpeople based on those standards, uninfluenced by
self-interest. When he pleaded with someone aboutsomething, he did it in all seriousness, often turning
red in the face. Even in his earnest remonstrance,
though, his compassion for others was always evident. When he talked with people in his office, his
voice echoed throughout the corridor, at times
encouraging or chiding, at other times erupting in
big-hearted laughter. One year and eight months havepassed since Dr. Fujita’s voice was last heard at
RERF.
In March 1968, Dr. Fujita was hired as a researchscientist of the Department of Statistics at ABCC
(now RERF). He was the first person to assume theposition of senior research scientist at RERF. After
serving as Assistant Chief of the Department of Statistics, he retired from RERF in December 2002,
upon reaching mandatory retirement age. SubseReturn to Table of Contents

quently, he was reemployed as a research scientist
at the Department of Statistics. He devoted his
efforts over 37 years to the research of ABCC and
RERF. His expertise in dosimetry was eagerly sought
after by various organizations. He served as a committee member for the Nuclear Safety Research
Association’s “Evaluation of Health Effects ofRadiation Exposure,” as a researcher for the National
Institute of Radiological Sciences’ “Study of Dose
Effect in Low-dose Region,” and as an expert member for the Japan Atomic Energy Research Institute’s“Low-dose Radiation Safety Evaluation Database,”among others. In 1995, he appeared on TV as a lecturer for a Hiroshima University extension lecture
series to talk about atomic bomb radiation dose.
Beforehand, he practiced his lecture over and overagain in his office, tripping over a word, and saying
to himself, ìIt may be better to explain it this way forviewers to readily understand.î In front of the camera on the day of shooting, Dr. Fujita calmly interacted with the announcer. When I said to him, “Itwent quite smoothly,” he responded with smile, “I
thrive under pressure.”
The foundation of RERF’s health risk assessment
RERF Update Volume 17, 2006

Human Interest Notes
is estimation of radiation dose (exposure variable).
It is undisputable that Dr. Fujita’s contributions
included his putting a great deal of effort toward thedevelopment and introduction of the different
dosimetry systems used at RERF. He played a rolein the U.S.-Japan joint reassessment of atomic bombradiation dosimetry, which started in 1981, as one of
the Japanese members, and greatly contributed to theestablishment of the Dosimetry System 1986 (DS86).
Even after the promulgation of DS86, he wasinvolved in efforts to collect exposed materials (tile,brick, concrete, iron, copper, etc.) in Hiroshima andNagasaki for analysis of the uncertainties in the estimate system, traveling to the collection sites as acollection supervisor. It is with a feeling of nostalgia for us now to look at the photographs taken in

Dr. Shoichiro Fujita collecting samples on the top of
Mt. Kompira in 1997

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26
November 1997 at the time of collection of concretecores from the buried antiaircraft bunker on the topof Mt. Kompira in Nagasaki. In creating the Japanese version of the recently published Dosimetry
System 2002 (DS02) report, Dr. Fujita cloisteredhimself in his home for two months to edit the Japanese translation despite his illness. This clearly shows
what he was like. He devoted himself singleheartedly to fulfill his responsibilities, leaving nothing unfinished.
There are simply too many stories to tell about
Dr. Fujita, who was loved by everybody. We had asmall party on the occasion of Dr. Fujita’s retirementin 2002. This photograph taken on that occasion
reminds me of several unforgettable scenes: Dr.
Fujita listening to messages from people at the party,
and Dr. Fujita breaking out in a large grin
after receiving abouquet of flowers.
At that time, nobody
knew that two years
later the time would
come to bid Dr.
Fujita a sorrowful
farewell. Dr. Fujita
passed away on
April 3, 2005 (Sunday). He was 63
years old. We mourn
Dr. Fujita’s untimely
Dr. Fujita at his farewell party death. May his soulin 2002
rest in peace.

RERF Update Volume 17, 2006

27

Facts and Figures

Facts and Figures
In the previous issue (volume 16 of the Update) we
had likened RERF’s vast Biosample Archive to “crownjewels.” Well, RERF’s “treasures” extend beyond thestored biosamples: RERF has a sizable collection ofhistorical documents, publications, and references as well.
This component of the RERF’s archive has been
recently reviewed and summarized by the Office of thePermanent Director, Mr. Takanobu Teramoto. The
salient features of this report are listed below andinclude the following archival elements: ABCC-RERF
Publications, RERF’s Database System, and the RERF
Library Archives.
ABCC-RERF Publications
There are seven distinct categories of publications
currently available for review by RERF researchers,
and with the exception of the RERF Newsletter and
RERF Annual Report, all are accessible by the outsidescientific community via RERF’s website.
The seven publication categories include: RERF’s
Research Protocols, ABCC-RERF Technical Report and
RERF Report series, Commentary and Review series,
the joint U.S.-Japan reports on the dosimetry reassessments of atomic bomb irradiation of Hiroshima/
Nagasaki Life Span Study (LSS) cohort members,
RERF Annual Reports, Newsletters, and its own journal, the Update.

1. Research Protocols (abstracts only) are available
for inspection on the web page. This number
includes 66. All protocols, past and present (approximately 550 in total since 1959) are available upon request by study participants andresearch collaborators.
2. ABCC-RERF Technical Reports and RERF Reports
are available on various studies that have been conducted from 1947 to present. There are some 3,679
items in this category, with approximately a third(1,146 out of the 3,679) processed under RERF’s
current review system. A series of LSS reports (21issues of a periodic update on analyses of the LSS
cohort) along with a comparable series of reports (9issues) on the Adult Health Study (AHS) cohort havebeen published and are available as well.
3. Commentary and Review series have been publishedon an intermittent basis in order to disseminate ideas,
stimulate discussion on given topics, and to solicit
comments from the research community at large on
RERF’s ongoing research.
4. U.S.-Japan reports on the reassessment of the atomic
bomb radiation dosimetry for Hiroshima andNagasaki are available and include the DS86 report(2 volumes) and the DS02 report (2 volumes). It
should be noted that the earlier T65D reports were
published as ABCC Technical Reports.
5. Annual Report series includes 69 issues and covers
the period from 1952 to present.
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6. Update journal focuses on current RERF’s
research activities and seeks to target both RERF
researchers and outside investigators alike. The series has 40 issues, covering the period from 1989 topresent.
7. Newsletter is an informational publication for bothformer and present RERF employees. There are 823
issues in the series and it covers theperiod from 1963 to present.
RERF Database System
The database includes the following seven partitioned databases: a core resource database, research anddocument databases, research information management
system, library and historical document databases, anda website-accessible database for the outside scientificcommunity and interested laypersons.
1. Core Resource Database consists of a variety of
research data, plus the inclusion of personal and confidential information. Due to the latter, access to thisdatabase is strictly limited to fully authorized RERF
staff members on a need-to-know basis.
2. Research Database serves as an essential, basic research tool for RERF researchers in carrying out avariety of analytical procedures on given datasets.
In contrast to the above listed “Resource Database”
datasets contained within this database have beenthoroughly scrubbed and are free of any/all personaland confidential information.
3. Document Resource System serves as an analytic
operations documentation resource.
4. Research Management Information System is dedicated to providing details on RERF’s publication
procedure, from the initial submission to the Scientific Reports Review Committee, through internal
review and authorization, to final journal submission.
5. Library Database contains electronic listing of current library holdings, including all scientific journals, textbooks, and references. In addition, Library
Database contains a general listing of procedures
for library patrons.
6. Historical Materials Database contains records pertaining to early ABCC-RERF research activities,
including microscopic-image slides, photographs,
and newspaper articles.
7. RERF website contains an assortment of researchdata from specific clinical and experimental studies
that are accessible and available for free downloading; e.g., mortality data, chromosome aberration
data, etc.
RERF Library Archives
RERF Library maintains approximately 39,000 reference items (specialized textbooks, references, andjournals) related to radiation effects research.
RERF Update Volume 17, 2006

Research Protocols and Publications

Research Protocols Approved in 2005
RP 1-05 Glaucoma Study in Atomic Bomb Survivors
Minamoto A, Tsukamoto H, Yokoyama T, Tsuiki E,
Uematsu M, Ogawa T, Mishima HK, Kitaoka T,
Nakashima E, Neriishi K, Hida A, Fujiwara S,
Akahoshi M
It is well known clinically that radiation exposure induces glaucoma. The relationship between
glaucoma and radiation in the Adult Health Study(AHS), however, is not consistent: The AHS Report
8 indicates a significant negative association between
incidence of glaucoma and radiation dose, while acataract study indicates no association between
radiation dose and glaucoma-associated findings, i.e.,
papilla atrophy and intraocular pressure. Both studies, however, are too incomplete to draw any conclusions about the relationship. This study was therefore planned.
All AHS subjects will be screened during theperiod from 2007 to 2009 with a visual field screener
and fundus photos, and those diagnosed by ophthalmologists as having abnormalities will be referredto the ophthalmology departments of the Hiroshima
and Nagasaki university hospitals, where detailed
ophthalmologic examinations will be conducted.
Copies of the data from the examination findings
will be collected and analyzed at RERF.

28
S, Cologne JB, Akahoshi M
Experimental and epidemiological studies reporta close relationship between inflammation and cancer. Because A-bomb survivors have radiation dosedependent increases of inflammatory biomarkers, wewill investigate the relationship between thebiomarkers and cancer incidence among 12,870
Adult Health Study participants followed from 1965
to 1999.
We will examine white blood cell counts (measured since 1958), erythrocyte sedimentation rate(since 1958), alpha 1 and alpha 2 globulins (since1985), and sialic acid (1988–1992) as parameters.
We will obtain cancer incident data for 1965–1999
from the Hiroshima and Nagasaki tumor registries.
We will perform multivariate analysis including
inflammatory diseases, smoking, alcohol consumption, and body mass index as risk factors. To assess
inflammation effects on cancer development we will
apply first principal component analysis, growth
curve models, the Cox regression model, and a quasimechanistic bystander effect model (indirect effectmodel) to the data.

RP 2-05 Could Genetic Factors Cause Population Bias among Proximal A-bomb Survivors?—A Test of Whether the Same Genetic
Factors Are Risk Factors for High Inflammatory Status and Myocardial Infarction among
A-bomb Survivors 40–50 Years Later
Fujiwara S, Suzuki G, Ohishi W, Yamada M,
Akahoshi M, Cologne JB
This study will test whether genetic factors relating to inflammatory responsiveness altered the fateof survivors upon radiation injury, burn, and infection after atomic bombing and caused a population
bias among highly exposed A-bomb survivors. Subjects are all the 1,100 individuals who participatedin the first cycle of clinical Adult Health Study
examinations and who were exposed when young(<30 years of age at the time of bombings) to at least
1 Gy of radiation, and 1,100 of their sex-, age-, andcity-matched <5 mGy exposed controls. The LTA andTLR2 gene-polymorphism will be typed using
genomic DNA extracted from cover-slipped peripheral blood smear samples.
RP 3-05 Inflammation and Cancer Incidencein Atomic Bomb Survivors
Neriishi K, Hsu W-L, Nakashima E, Little MP,
Tatsukawa Y, Nishi N, Soda M, Yamada M, Fujiwara
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RERF Update Volume 17, 2006

Research Protocols and Publications

Recent Publications(Japanese): the original article is in Japanese.
(Bilingual): the original article is in both English and Japanese.

Akahoshi M, Hida A, Imaizumi M, Soda M, Maeda
R, Ichimaru S, Nakashima E, Seto S, Yano K. Basiccharacteristics of chronic hypotension cases: A
longitudinal follow-up study from 1958 through1999. Hypertension Research 2006 (January);29(1):1-7. (RERF Report 11-04)
Asia Pacific Cohort Studies Collaboration (RERF:
Nakachi K). A comparison of the associations between risk factors and cardiovascular disease in
Asia and Australasia. European Journal of Cardiovascular Prevention and Rehabilitation 2005 (October); 12(5):484-91.
Asia Pacific Cohort Studies Collaboration (RERF:
Nakachi K). Joint effects of systolic blood pressure and serum cholesterol on cardiovascular disease in the Asia Pacific region. Circulation 2005
(November 29); 112(22):3384-90.
Asia Pacific Cohort Studies Collaboration (RERF:
Nakachi K). Smoking and elevated blood pressure
are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an
overview of 26 cohorts involving 306 620 participants. Stroke 2005 (July); 36(7):1360-5.
Asia Pacific Cohort Studies Collaboration (RERF:
Nakachi K). A comparison of lipid variables aspredictors of cardiovascular disease in the Asia
Pacific region. Annals of Epidemiology 2005
(May); 15(5):405-13.
Asia Pacific Cohort Studies Collaboration (RERF:
Nakachi K). Does sex matter in the associations
between classic risk factors and fatal coronary
heart disease in populations from the Asia-Pacificregion? Journal of Women’s Health 2005 (November 9); 14(9):820-8.
Bennett BG.. Responsibility beyond 60 years. Science 2005 (September 9); 309:1649.
Bennett BG, Waldren CA. 60 years since atomic
bombings of Hiroshima and Nagasaki: Radiation
effects research at RERF. Radiation Research
2005; 164:235-6.
Chayama K(editor-author), Ohishi W, Imamura M.
An In-depth Look at Patient Treatment for Chronic
Hepatitis B and C. Tokyo: Nankodo; 2005
(July),148 p. (Japanese)

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29
Cullings HM, Egbert SD, Maruyama T, Hoshi M,
Fujita S. Comparison of TLD measurements with
DS86 and DS02. Young RW, Kerr GD, eds. Reassessment of the Atomic Bomb Radiation Dosimetry for Hiroshima and Nagasaki—Dosimetry
System 2002 (DS02). Hiroshima: Radiation
Effects Research Foundation; 2005 (December),
pp 395-455.
Cullings HM, Fujita S, Hoshi M, Egbert SD, Kerr
GD. Alignment and referencing of maps and aerial
photographs. Young RW, Kerr GD, eds. Reassessment of the Atomic Bomb Radiation Dosimetryfor Hiroshima and Nagasaki—Dosimetry System
2002 (DS02). Hiroshima: Radiation Effects
Research Foundation; 2005 (December), pp 261333.
Cullings HM, Fujita S, Preston DL, Grant EJ,
Shizuma K, Hoshi M, Maruyama T, Lowder WM.
The RERF dosimetry measurements database.
Young RW, Kerr GD, eds. Reassessment of theAtomic Bomb Radiation Dosimetry for Hiroshima
and Nagasaki—Dosimetry System 2002 (DS02).
Hiroshima: Radiation Effects Research Foundation; 2005 (December), pp 334-61.
Cullings HM, Fujita S, Watanabe T, Yamashita T,
Tanaka K, Endo S, Shizuma K, Hoshi M, Hasai
H. Sample collection and documentation. Young
RW, Kerr GD, eds. Reassessment of the Atomic
Bomb Radiation Dosimetry for Hiroshima andNagasaki—Dosimetry System 2002 (DS02).
Hiroshima: Radiation Effects Research Foundation; 2005 (December), pp 223-60.
Egbert SD, Cullings HM. Graphical comparisons ofmeasurements and calculations for neutrons andgamma rays. Young RW, Kerr GD, eds. Reassessment of the Atomic Bomb Radiation Dosimetryfor Hiroshima and Nagasaki—Dosimetry System
2002 (DS02). Hiroshima: Radiation Effects
Research Foundation; 2005 (December), pp 864920.
Eguchi H, Nakachi K. Smoking as a risk factor forpancreatic cancer. Nippon Rinsho [Japanese Journal of Clinical Medicine] 2006 (January 28);
64:10-3. (Japanese)
Fujiwara S, Sone T, Yamazaki K, Yoshimura N,
Nakatsuka K, Masunari N, Fujita S, Kushida K,
Fukunaga M. Heel bone ultrasound predicts nonspine fracture in Japanese men and women.
Osteoporosis International 2005 (December);
16(12):2107-12. (RERF Report 18-04)

RERF Update Volume 17, 2006

Research Protocols and Publications
Hakoda M, Masunari N, Yamada M, Fujiwara S,
Suzuki G, Kodama K, Kasagi F. Serum uric acidconcentration as a risk factor for cardiovascularmortality: A longterm cohort study of atomic bomb
survivors. Journal of Rheumatology 2005 (May);32(5):906-12. (RERF Report 1-03)
Hakoda M, Oiwa H, Kasagi F, Masunari N, YamadaM, Suzuki G, Fujiwara S. Mortality of rheumatoid arthritis in Japan: a longitudinal cohort study.
Annals of Rheumatic Diseases 2005 (October);
64(10):1451-5. (RERF Report 19-04)
Hamai Y, Matsumura S, Matsusaki K, Kitadai Y,
Yoshida K, Yamaguchi Y, Imai K, Nakachi K, Toge
T, Yasui W. A single nucleotide polymorphism inthe 5' untranslated region of the EGF gene isassociated with occurrence and malignant progression of gastric cancer. Pathology 2005; 72:133-8.
Hamajima N, Mutoh M, Eguchi H, Honda H. Minimal sizes of cases with a susceptible genotype andminimal odds ratios among susceptible individuals in case-control studies. Asian Pacific Journalof Cancer Prevention 2005; 6:165-9.
Hayashi T, Imai K, Morishita Y, Hayashi I, Kusunoki
Y, Nakachi K. Identification of the NKG2D
haplotypes associated with natural cytotoxic
activity of peripheral blood lymphocytes and cancer immunosurveillance. Cancer Research 2006
(January 1); 66(1):563-70.
Hayashi T, Morishita Y, Hayashi I, Masuda M, Fujita
K, Kusunoki Y, Jitsukata K, Nakachi K. Rapid andmulti-sample determination of reactive oxygen
species in human sera. Nihon Rinsho Kensa Jidoka
Gakkai Kaishi [Japanese Journal of ClinicalLaboratory Automation] 2005; 30(3):216-20.
(Japanese)
Hida A, Akahoshi M, Toyama K, Imaizumi M, Soda
M, Maeda R, Ichimaru S, Nakashima E, Eguchi
K. Do glucose and lipid metabolism affect cancer
development in Nagasaki atomic bomb survivors?
Nutrition and Cancer 2005; 52(2):115-20. (RERF
Report 16-04)
Huang M, Ida H, Kamachi M, Iwanaga N, Izumi Y,
Tanaka F, Aratake K, Arima K, Tamai M, Hida A,
Nakamura H, Origuchi T, Kawakami A, Ogawa
N, Sugai S, Utz PJ, Eguchi K. Detection of
apoptosis-specific autoantibodies directed against
granzyme B-induced cleavage fragments of the
SS-B (La) autoantigen in sera from patients withprimary Sjögren’s syndrome. Clinical and Experimental Immunology 2005 (October); 142(1):14854.
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30
Imaizumi M, Usa T, Tominaga T, Akahoshi M,
Ashizawa K, Ichimaru S, Nakashima E, Ishii R,
Ejima E, Hida A, Soda M, Maeda R, Nagataki S,
Eguchi K. Long-term prognosis of thyroid nodulecases compared with nodule-free controls in
atomic bomb survivors. Journal of Clinical Endocrinology and Metabolism 2005 (September);90(9):5009-14. (RERF Report 8-04)
Imaizumi M, Usa T, Tominaga T, Neriishi K,
Akahoshi M, Nakashima E, Ashizawa K, Hida A,
Soda M, Fujiwara S, Yamada M, Ejima E,
Yokoyama N, Okubo M, Sugino K, Suzuki G,
Maeda R, Nagataki S, Eguchi K. Radiation doseresponse relationships for thyroid nodules andautoimmune thyroid diseases in Hiroshima andNagasaki atomic bomb survivors 55-58 years
after radiation exposure. Journal of the American
Medical Association 2006 (March); 295(9):101122. (RERF Report 1-05)
Inai K, Shimizu Y, Kawai K, Tokunaga M, Soda M,
Mabuchi K, Land CE, Tokuoka S. A pathology
study of malignant and benign ovarian tumors
among atomic-bomb survivors—Case series
report. Journal of Radiation Research 2006;
47(1):49-59. (RERF Report 4-05)
Ito R, Oue N, Yoshida K, Kunimitsu K, Nakayama
H, Nakachi K, Yasui W. Clinicopathological significant and prognostic influence of cadherin-17
expression in gastric cancer. Virchows Archiv 2005
(October); 447(4):717-22.
Johnell O, Kanis J, Oden A, Johansson H, Laet CD,
Delmas P, Eisman JA, Fujiwara S, Kroger H,
Mellstrom D, Meunier PJ, Melton LJ, O’Neill TO,
Pols H, Reeve J, Silman A, Tenenhouse A. Predictive value of BMD for hip and other fractures.
Journal of Bone and Mineral Research 2005;
20(7):1185-94.
Kambe M, Matsumura M, Suyama A, Nishi N,
Tsujiyama S, Hyoudou M, Yunokawa M,
Murakami H, Urabe A, Yamane T, Arai H, Ono H,
Watanabe T, Oda T, Soramoto E, Mukai M,
Shimizu H, Nakamura A, Shimamura E, Yoshida
Y, Usui S. Report on the results of the fifteenth
medical examination of atomic bomb survivors
resident in North America. Hiroshima Igaku [Journal of the Hiroshima Medical Association] 2006
(January); 59(1):23-48. (Bilingual)Kanda K, Suyama A, Furuse N, Tamashiro H.
e-Learning in public health: Development ofSupercourse-Japan. Hoken Iryo Kagaku [Journalof National Institute of Public Health] 2005;
54(3):182-6. (Japanese)
RERF Update Volume 17, 2006

Research Protocols and Publications
Kanzaki H, Hanafusa H, Yamamoto H, Yasuda Y,
Imai K, Yano M, Aoe M, Shimizu N, Nakachi K,
Ouchida M, Shimizu K. Single nucleotide polymorphism at codon 133 of the RASSF1 gene ispreferentially associated with human lung adenocarcinoma risk. Cancer Letters 2005 (August 24);
238(Issue 1):128-34.
Kerr GD, Shizuma K, Maruyama T, Cullings HM,
Komura K, Okumura Y, Egbert SD, Endo S.
Cobalt (60Co) activation. Young RW, Kerr GD, eds.
Reassessment of the Atomic Bomb Radiation
Dosimetry for Hiroshima and Nagasaki—Dosimetry System 2002 (DS02). Hiroshima: Radiation
Effects Research Foundation; 2005 (December),
pp 456-81.

31
ity. Radiation Research 2005; 164:618-26. (RERF
Report 6-05)
Kondrashova TV, Neriishi K, Ban S, Ivanova TI,
Krikunova LI, Shentereva NI, Smirnova IA,
Zharikova IA, Konova MV, Taira S, Tsyb AF. Frequency of hemochromatosis gene (HFE) mutations
in Russian healthy women and patients withestrogen-dependent cancers. Biochimica etBiophysica Acta 2006 (January); 1762(1):59-65.
Kubo Y, Yamaoka M, Kusunoki Y. A preliminary
study measuring the number of T-cell receptorrearrangement excision circles (TRECs) in peripheral blood T-cell population of A-bomb survivors
and control populations. Cytometry Research 2006
(March); 16(1):33-41.

Kerr GD, Young RW, Cullings HM, Christy RF.
Bomb parameters. Young RW, Kerr GD, eds.
Reassessment of the Atomic Bomb Radiation
Dosimetry for Hiroshima and Nagasaki—Dosimetry System 2002 (DS02). Hiroshima: Radiation
Effects Research Foundation; 2005 (December),
pp 42-61.

Kuraoka K, Matsumura S, Sanada Y, Nakachi K, Imai
K, Eguchi H, Matsusaki K, Oue N, Nakayama H,
Yasui W. A single nucleotide polymorphism in theextracellular domain of TRAIL receptor DR4 at
nucleotide 626 in gastric cancer patients in Japan.
Oncology Reports 2005 (August); 14(2):465-70.

Kishikawa M, Koyama K, Iseki M, Kobuke T,
Yonehara S, Soda M, Ron E, Tokunaga M, Preston
DL, Mabuchi K, Tokuoka S. Histologic characteristics of skin cancer in Hiroshima and Nagasaki:
Background incidence and radiation effects. International Journal of Cancer 2005 (November);117(3):363-9. (RERF Report 20-04)

Kyoizumi S, Kusunoki Y, Hayashi T, Hakoda M,
Cologne JB, Nakachi K. Individual variation ofsomatic gene mutability in relation to cancer susceptibility: Prospective study on erythrocyte
glycophorin A gene mutations of atomic bomb
survivors. Cancer Research 2005 (June);
65(12):5462-9. (RERF Report 5-04)

Kodama K, Kasagi F, Nishi N, Sugiyama H, Soda
M. Large-scale cohort and local cancer registry.
Cohort of atomic bomb survivors in Hiroshima andNagasaki. JACR Monograph 2005; No.10:39-42.
(Japanese)

Maruyama T, Cullings HM, Hoshi M, Nagatomo T,
Kumamoto Y, Kerr GD. Thermoluminescence dosimetry for gamma rays. Young RW, Kerr GD, eds.
Reassessment of the Atomic Bomb Radiation
Dosimetry for Hiroshima and Nagasaki—Dosimetry System 2002 (DS02). Hiroshima: Radiation
Effects Research Foundation; 2005 (December),
pp 362-94.

Kodama K, Shigematsu I (Chairperson). Health andmedical care for the radiation exposed and the rolesof Hiroshima—Messages from the 60th anniversary of atomic bombings. Report on “International
Collaborative Symposium on Medical Care for the
Radiation-exposed” to commemorate the 60th
anniversary of the atomic bombings. Hiroshima:
Hiroshima International Council for Health Careof the Radiation-exposed; 2006 (March): 9-18.
(Japanese)
Kodama K, Shimizu Y, Okubo T. Late health effects
in the atomic bomb survivors. Acta Medica
Nagasakiensia 2005; 50:15-8.
Kodama Y, Ohtaki K, Nakano M, Hamasaki K, Awa
AA, Lagarde F, Nakamura N. Clonally expanded
T-cell populations in atomic bomb survivors do
not show excess levels of chromosome instabilReturn to Table of Contents

Matsumura S, Oue N, Nakayama H, Kitadai Y,
Yoshida K, Yamaguchi Y, Imai K, Nakachi K,
Matsusaki K, Chayama K, Yasui W. A single nucleotide polymorphism in the MMP-9 promoter
affects tumor progression and invasive phenotype
of gastric cancer. Journal of Cancer Research andClinical Oncology 2005 (September); 131:19-25.
Morita N, Takamura N, Ashizawa K, Shimasaki T,
Yamashita S, Okumura Y. Measurement of thewhole-body 137 Cs in residents around theChernobyl nuclear power plant. Radiation Protection Dosimetry 2005; 113(3):326-9.
Nakamura N. Effect of atomic-bomb radiation tohumans: 60 years after the event. Shunin-sha NewsRERF Update Volume 17, 2006

Research Protocols and Publications[Radiation Protection Supervisor Newsletter] 2005
(September); 11:2-6. (Japanese)
Nakamura N. 60 years after A-bombings and radiation risk: Possible mechanisms of radiation-related
leukemia. Yakugaku Zasshi [Journal of the Pharmaceutical Society of Japan] 2005 (September);
125(2):69-72. (Japanese)
Nakamura N. Radiation and leukemia: Existence ofpeople at high risk and low risk. Hoshasen Seibutsu
Kenkyu [Radiation Biology Research Communications] 2005; 40(3):231-44. (Japanese)
Nakamura N, Cullings HM, Kodama Y, Wada T,
Miyazawa C, Lee K, Awa AA. A method to differentiate between the levels of ESR signals inducedby sunlight and by ionizing radiation in teeth fromatomic bomb survivors. Radiation Research 2006
(March); 165(3):359-64. (RERF Report 14-05)
Nakashima E, Neriishi K, Minamoto A. A reanalysis of atomic-bomb cataract data, 2000-2002: A
threshold analysis. Health Physics 2006 (February); 90(2):154-60. (RERF Report 26-03)
Nawata H, Soen S, Takayanagi R, Tanaka I, Takaoka
K, Fukunaga M, Matsumoto T, Suzuki Y, Tanaka
H, Fujiwara S, Miki T, Sagawa A, Nishizawa Y,
Seino Y. Guidelines on the management and treatment of glucocorticoid-induced osteoporosis of theJapanese Society for Bone and Mineral Research(2004). Journal of Bone and Mineral Metabolism
2005; 23(2):105-9.
Nishi N, Kodama K. Health effects of radiation
among atomic bomb survivors. Byori to Rinsho[Pathology and Clinical Medicine] 2005 (July);23(7):757-63. (Japanese)
Nishi N, Oguri S, Onoda T, Nohara M, Inoue H,
Okayama A. Knowledge of smoking-related risks
and opinions on tobacco control by smoking status and education level in Japan. Japanese Journalof Public Health 2005 (November); 52(11):96270.
Nishi N, Sugiyama H, Kasagi F, Katayama H,
Kodama K, Arita K, Arihiro K, Ogawa T, Sonobe
H, Sasaki N, Daimaru H, Takada Y, Takeshima Y,
Tanaka H, Taniyama K, Nakayama H, Nanba K,
Nishida T, Hayakawa N, Hayashi Y, Fukuhara T,
Fujihara M, Matsuura H, et al. The trend in prostate cancer in Hiroshima Prefecture as seen fromtissue registry. Hiroshima Igaku [Journal of theHiroshima Medical Association] 2005 (October);
58(10):580-3. (Japanese)

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32
Nishi N, Sugiyama H, Kasagi F, Katayama H,
Kodama K, Kuwabara M, Arita K. Current situation of and challenge for cancer registries in
Hiroshima City and Hiroshima Prefecture. JACR
Monograph 2005; No.10:75-8. (Japanese)
Nishi N, Sugiyama H, Kasagi F, Katayama H,
Kodama K, Kuwabara M, Arita K, Yasui W.
Numerical changes in prostate tumor registrationin Hiroshima Prefecture, as seen from tissue registry. JACR Monograph 2006 (March 31);
No.11:60-4. (Japanese)
Ogawa T, Hayashi T, Tokunou M, Nakachi K, Trosko
JE, Chang CC, Yorioka N. Suberoylanilidehydroxamic acid enhances gap junctional intercellular communication via acetylation of histone
containing connexin 43 gene locus. Cancer
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Packeisen J, Nakachi K, Boecker W, Brandt B,
Buerger H. Cytogenetic differences in breast cancer samples between German and Japanesepatients. Journal of Clinical Pathology 2005
(October); 58(10):1101-3.
Preston DL, Pierce DA, Shimizu Y. Response to letter on curvature in the dose response of the Life
Span Study cancer mortality data by Linda Walshet al. (Letter to the editor). Radiation Research2005 (April); 163(4):477.
Ron E, Ikeda T, Preston DL, Tokuoka S. Male breast
cancer incidence among atomic bomb survivors.
Journal of the National Cancer Institute 2005
(April); 97(8):603-5. (RERF Report 13-04)
Ron E, Preston RJ, Tokuoka S, Funamoto S, Nishi
N, Soda M, Mabuchi K, Kodama K. Solid cancer
incidence among atomic bomb survivors: Preliminary data from a second follow-up. Acta Medica
Nagasakiensia 2005; 50:23-5.
Santoro RT, Barnes JM, Azmy YY, Egbert SD, Kerr
GD, Cullings HM. Nagasaki factory worker shielding. Young RW, Kerr GD, eds. Reassessment of
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Sauvaget C, Lagarde F, Nagano J, Soda M, Koyama
K, Kodama K. Lifestyle factors, radiation and gastric cancer in atomic-bomb survivors (Japan). Cancer Causes and Control 2005 (September);16(7):773-80. (RERF Report 12-04)

RERF Update Volume 17, 2006

Research Protocols and Publications
Sauvaget C, Nagano J, Yamada M. Fat and proteinfrom vegetable source and the risk of cerebral
infarction death in Japanese. Journal of Nutrition,
Health & Aging 2005; 9(3):155.
Sharp GB, Lagarde F, Mizuno T, Sauvaget C,
Fukuhara T, Allen NE, Suzuki G, Tokuoka S.
Relationship of hepatocellular carcinoma to soya
food consumption: A cohort-based, case-control
study in Japan. International Journal of Cancer
2005 (June); 115(2):290-5. (RERF Report 25-03)
Straume T, Marchetti AA, Egbert SD, Roberts JA,
Men P, Fujita S, Shizuma K, Hoshi M. 36Cl measurements in the United States. Young RW, Kerr
GD, eds. Reassessment of the Atomic Bomb
Radiation Dosimetry for Hiroshima andNagasaki—Dosimetry System 2002 (DS02).
Hiroshima: Radiation Effects Research Foundation; 2005 (December), pp 497-538.

33
Tahara E. MHLW Grants: FY2003-2005 Report ofThird Term Comprehensive Control Research forCancer. Development Study on Comprehensive
Cancer Prevention Publications and Reprints of
Research Results. 2006 (March), 553 p. (Japanese)
Tahara E Jr, Tahara H, Kanno M, Naka K, Takeda Y,
Matsuzaki T, Yamazaki R, Ishihara H, Yasui W,
Barrett JC, Ide T, Tahara E. G1P3, an interferon
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in gastric cancer cell line TMK-1 cell. Cancer Immunology, Immunotherapy 2005 (August);
54(8)729-40.
Wong FL, Yamada M, Tominaga T, Fujiwara S,
Suzuki G. Effects of radiation on the longitudinal
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bomb survivors. Radiation Research 2005
(December); 164(6):820-7. (RERF Report 3-05)

Sueoka E, Sueoka N, Iwanaga K, Sato A, Suga K,
Hayashi S, Nagasawa K, Nakachi K. Detection ofplasma hnRNP B1 mRNA, a new cancer
biomarker, in lung cancer patients by quantitative
real-time polymerase chain reaction. Lung Cancer 2005 (April); 48(1):77-83.

Yamada M, Naito K, Kasagi F, Masunari N, Suzuki
G. Prevalence of atherosclerosis in relation toatomic bomb radiation exposure: An RERF Adult
Health Study. International Journal of Radiation
Biology 2005 (November); 81(11):821-6. (RERF
Report 2-04)

Sugiyama H, Nishi N, Kasagi F, Katayama H,
Kodama K, Fujihara M, Ito C, Fukuhara T,
Matsuura H, Sugiyama S, Takata K, Santo T,
Miwata H, Kurisu Y, Yoshinaga J, Iyoda K,
Yamamoto M, Kuwabara M, Hiramatsu K, Arita
K, Yasui W. Trend in incidence rate of breast cancer in Hiroshima City. Hiroshima Igaku [Journalof the Hiroshima Medical Association] 2005
(November); 58(11):639-42. (Japanese)

Yamada M, Wong FL, Fujiwara S, Tatsukawa Y,
Suzuki G. Smoking and alcohol habits as risk factors for benign digestive diseases in a Japanese
population: The Radiation Effects Research Foundation Adult Health Study. Digestion 2005 (July);
71(4):231-7. (RERF Report 22-04)

Tahara E. Growth factors and oncogenes in gastrointestinal cancers. Meyers RA, ed. Encyclopedia of Molecular Cell Biology and Molecular
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Germany: Wiley-VCH Verlag GmbH & Co.
KGaA; 2005 (May), pp 1-31.
Tahara E, Lotan R. RUNX3 and retinoic acid receptor b DNA methylation as novel targets for gastriccancer therapy. Current Cancer Therapy Reviews
2005; 1(2):139-44.
Tahara E. MHLW Grants: FY2005 Report of Third
Term Comprehensive Control Research for Cancer. Development Study on Comprehensive Cancer Prevention Publications and Reprints of
Research Results. 2006 (March), 199 p. (Japanese)

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Yamaguchi A, Tazuma S, Nishioka T, Ohishi W,
Hyogo H, Nomura S, Chayama K. Hepatitis C
virus core protein modulates fatty acid metabolism and thereby causes lipid accumulation in theliver. Digestive Diseases and Sciences 2005 (July);
50(7):1361-71.
Yamamoto H, Hanafusa H, Ouchida M, Yano M,
Suzuki H, Murakami M, Aoe M, Shimizu N,
Nakachi K, Shimizu K. Single nucleotide polymorphisms in the EXO1 gene and risk of colorectal
cancer in a Japanese population. Carcinogenesis
2005 (November); 26(2):411-6.
Yasui W, Oshimura M, Igarashi K, Ito H, Tahara E.
Cancer and epigenetics—basic research and clinical implications: Joint Meeting of the FourteenthInternational Symposium of the Hiroshima Cancer Seminar and the Eighth Meeting of the Tottori
Bioscience Promotion Foundation, October 2004.
Cancer Science 2005 (April); 96(4):245-8.

RERF Update Volume 17, 2006

34

Research Protocols and Publications
Young RW, Egbert SD, Cullings HM, Kerr GD,
Imanaka T. DS02 free-in-air neutron and gamma
tissue kerma relative to DS86. Young RW, Kerr
GD, eds. Reassessment of the Atomic Bomb
Radiation Dosimetry for Hiroshima andNagasaki—Dosimetry System 2002 (DS02).
Hiroshima: Radiation Effects Research Foundation; 2005 (December), pp 848-57.
Yuasa Y, Nagasaki H, Akiyama Y, Sakai H, Nakajima
T, Ohkura Y, Takizawa T, Koike M, Tani M, Iwai
T, Sugihara K, Imai K, Nakachi K. Relationshipbetween CDX2 gene methylation and dietary factors in gastric cancer patients. Carcinogenesis 2005
(October); 26(1):193-200.

Return to Table of Contents

Publication Using RERF Data
The following publication represents research done by nonRERF scientists based on the data publicly available from
RERF.

Zhang W, Muirhead CR, Hunter N. Age-at-exposure
effects on risk estimates for non-cancer mortality
in the Japanese atomic bomb survivors. Journalof Radiological Protection 2005 (December);25(4):393-404.

RERF Update Volume 17, 2006