Table of Contents
From the Editors ......................................................................................................................................... 1
RERF NewsThe 44th Board of Directors Meeting ................................................................................................... 1
Staff News ............................................................................................................................................. 4
Visiting Scientists .................................................................................................................................. 5
Visiting Student Researchers ................................................................................................................ 5
2009 Distinguished Lecture Series ....................................................................................................... 6
Awards Received by RERF Scientists .................................................................................................. 6
Conference and Workshop Reports
Late Health Effects of Ionizing Radiation: Bridging the Experimental andEpidemiologic Divide, by Evan B. Douple .................................................................................... 10
Dose Uncertainty Workshop, by Harry M. Cullings ........................................................................... 12International Symposium Based on Radiation Research Partnership, by Kotaro Ozasa .................... 13
Science Article
Chromosome Instability in Peripheral Blood T Lymphocytes from A-bomb
Survivors—In Vivo and In Vitro Studies, by Kanya Hamasaki and Yoshiaki Kodama .................. 14
Human Interest Notes
Participating in the Health Examination/Consultation Project for A-bomb Survivors
Living in South Korea, by Masazumi Akahoshi ............................................................................. 21
Work at the Nursing Sections in Hiroshima and Nagasaki ................................................................. 23
In Memoriam ...................................................................................................................................... 25
Facts and Figures
RERF Staff’s Strengths Demonstrated at Open House Events, by Takanobu Teramoto .................... 26
DS02 Errata ......................................................................................................................................... 27
Research Protocols and Publications
Research Protocols Approved in April–September 2009 .................................................................... 28
Recent Publications ............................................................................................................................. 30

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: Evan B. Douple, 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

1

From the Editors, RERF News

From the Editors
Welcome back!
Cool days and evenings have returned to Hijiyama,
and the RERF tennis court is quiet due to the shorter
daylight hours. The employees are fitting Bonenkai
into their busy end-of-the-year calendars and we allfind ourselves reflecting back on highlights of thepast year before we face the start of 2010.
In this issue we feature highlights of RERF’s
successful Open Houses held in the Hiroshima andNagasaki laboratories. Those annual events areimportant “windows” to the public and the A-bomb
survivors, enabling the visitors to learn more about
our research activities and to afford RERF researchscientists the opportunity to explain important results.
We were especially pleased to see many young
school-age children attending and actively participating. As in the past, the RERF staff work hard toprovide interesting displays and demonstrations that
communicate the RERF mission and accomplishments while acknowledging the contributionsof the A-bomb survivors and the collaborating
scientists. Please read more about those events in
Facts and Figures.
This issue also features a scientific article by
one of RERF’s young research scientists, Kanya
Hamasaki, who recently joined the Department of

Genetics. The article reviews recent studies of chromosome instability in peripheral blood lymphocytes
by Dr. Hamasaki and his collaborators.
RERF is starting a new research study of theeffects of radiation on the natural aging of theimmunological system. The large, five-year study
involves exciting collaborations between RERF
scientists and a number of scientists in researchlaboratories in the U.S. and Japan. With the additional
funding provided by the U.S. National Institute ofAllergy and Infectious Diseases, RERF scientists
hope to extend the Department of Radiobiology/
Molecular Epidemiology’s previous findings to a
new level for a better understanding of the role ofimmunology in the development of human diseases
in an aging population. Details of the study will be
described in the next issue of Update.
We were pleased to receive a note from Kenji Joji,a former Translation Section chief who served
both ABCC and RERF (1953–1989). He said heespecially was pleased to read in Update that the
Adult Health Study had successfully completed its
50th anniversary and he remembered well theimportant role that Seymour Jablon had played indeveloping the unified study programs at ABCC. As
always, drop us a line to let us know what articles
you would like to read about in future issues.
Ja, mata!

Evan B. Douple
Editor-in-Chief

Open House 2009, Hiroshima Laboratory

Yuko Ikawa
Technical Editor

44th Meeting of RERF’s Board of Directors Convened in Hiroshima
Two-stage Approach for Change of Status to Public-interest
Incorporated Foundation Approved
The 44th meeting of the Board of Directors washeld in the Auditorium at Hiroshima RERF on June
24 and 25, 2009. On behalf of the U.S. and Japanese
governments, Dr. Patricia R. Worthington, Director,
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Office of Health and Safety, Office of Health, Safety
and Security, U.S. Department of Energy and Dr.
Kaoru Manabe, Deputy Director, General Affairs
Division, Health Service Bureau, Japanese Ministry
RERF Update Volume 20, Issue 2, 2009

RERF Newsof Health, Labour and Welfare, delivered opening
addresses.
The participants engaged in active discussions on
the handling of future research plans, an issue
reviewed by RERF in response to the Senior Review
Panel’s recommendations made in June last year,
RERF’s study achievements thus far and theirevaluation, and how studies at RERF should be
carried out in the future. In relation to reform of the
public-interest corporation system, regarding which
new laws were implemented in December 2008,
RERF, designated an exceptional juridical person,
is aiming at completion of the transition process intoa public-interest incorporated foundation within thenext five years. RERF representatives explained thenecessary procedures involved in the future andrequested relevant advice. The visiting directors
stated that coordination with the U.S. and Japanese
governments and close contact among all the directors would be important. RERF’s future vision,
which has been discussed many times as one of thefoundation’s top priorities, was, together with study
details, once again debated passionately at themeeting.
Dr. Toshiteru Okubo, RERF Chairman, opened
the meeting with his status report for RERF, reportingon 1) the Scientific Council’s review of the foundation’s study program with a focus on the Departmentof Radiobiology/Molecular Epidemiology andthe Department of Genetics, 2) initiation of reexamination of records of exposure locations andshielding status using original records including
personal interview sheets, in response to the
Scientific Council’s support of initiation of review
of issues involving individual dosimetry, 3) conductof a staff training program initiated in November
2008 to improve staff morale/abilities and enable
them to respond to the changing work environmentand diversification, given the need for RERF toreview its activities and reform its organization, and4) the lack of space and funds for maintenance of
biological specimens.
In terms of international collaborations, participation in international collaborative activities,
acceptance of visitors from overseas for facility tours
and training, and partnership activities were reported.
As for public relations activities for disseminationof research-related information both in Japan andabroad, it was reported that further effort is being
made to enhance such dissemination of informationand establishment of friendly ties with the mass
media, aiming at providing scientific information to
non-RERF people in a readily understandable
manner.
The FY2008 research activities report, settlementof accounts and audit reports, as well as the FY2009
research activity plans were approved as presented.
The FY2009 working budget, which is almost
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2
identical to that of the previous year, was also
approved.
As for responses to the Senior Review Panel’s
recommendations, reports were made, as suggestedby the Board at its previous year’s meeting, on threemajor items: future research plans with a focus on
five-year research plans and project-type research
management, review of use of biospecimens, andexpansion of international collaborative projects.
As for change of status to a public-interest
incorporated foundation (PIIF), an important issue
related to RERF’s future direction, a two-stage
approach, involving application for recognition of
the draft Articles of Incorporation from the competentadministrative agencies by around July 2010 and
subsequent application for recognition of change ofstatus into a PIIF from the Cabinet Office, wasadopted. With this, it was formally approved that an
application be made to the competent administrative
agencies in terms of method for selection of firstcouncilors and that relevant procedures for theselection process be taken.
As for the personnel-reduction issue, given thatmaintenance of research scientists is the top-priority
issue for continuation of the research program, thedirectors requested that RERF take actions tominimize effects of personnel reduction on research
activities, by securing the maximum number of
research scientists and making efforts from aninternational perspective to recruit young talented
researchers.
On the second day, Mr. Glenn S. Podonsky, Chief
Health, Safety and Security Officer, Office of theSecretary of Energy, U.S. Department of Energy, whoarrived in Hiroshima the previous night, delivered aspeech referring to U.S. President Obama’s inauguration, appointment of DOE Secretary Chu, andcontinuation of financial support to RERF despite
severe financial conditions in the United States. Mr.
Podonsky also stated that the U.S. and Japanese
governments will continue to cooperate in providing
research support to the foundation. Thereafter,
deliberations proceeded according to the program,and all items for deliberation and action wereapproved.
Lastly, the Board discussed the appointment ofofficers and others. The Board approved thereappointment of Chairman Toshiteru Okubo, Vice
Chairman Roy E. Shore, Permanent Director
Takanobu Teramoto, and Visiting Director Yasuhito
Sasaki, whose four-year terms of office were due for
expiration at the end of June. Dr. Shelley A. Hearne(Managing Director, Health and Human Services
Policy, The Pew Charitable Trusts) was appointed
as director to succeed Dr. John E. Burris. The Board
approved that the term of office of Mr. David
Williams, supervisor, be extended for another three
years. As for scientific councilors, reappointment of
RERF Update Volume 20, Issue 2, 2009

3

RERF NewsDr. Sally A. Amundson, who had been appointed tocomplete her predecessor’s term of office, andappointment of Dr. Kazuo Sakai (Director, ResearchCenter for Radiation Protection, National Instituteof Radiological Sciences) as successor to Dr. Ohtsura
Niwa were approved.
The two-day meeting was concluded with thedecision that the next meeting will be held in
Nagasaki over the three days of June 21–23, 2010.
List of Participants
Directors:
Dr. Toshiteru Okubo, Chairman
Dr. Roy E. Shore, Vice Chairman and Chief ofResearch
Mr. Takanobu Teramoto, Permanent Director
Mr. Masaaki Kuniyasu, Former Ambassador
Extraordinary and Plenipotentiary to the
Republic of Portugal
Dr. Yasuhito Sasaki, Executive Director, Japan
Radioisotope Association
Dr. Senjun Taira, Permanent Director, Japanese
Quarantine Association
Mr. James W. Ziglar, Former Sergeant at Arms of
the United States Senate
Dr. James D. Cox, Professor and Head, Division ofRadiation Oncology, The University of Texas
M.D. Anderson Cancer Center
Dr. John E. Burris, President, Burroughs Wellcome
FundSupervisors:
Mr. Takashi Kohno, CPA/licensed Tax Accountant,
Hiroshima General Law/Accounting Office
Mr. David Williams, Senior Financial Advisor,
National Academy of Sciences

Co-chairman Scientific Council:
Dr. Katsushi Tokunaga, Professor, Department of
Human Genetics, Division of International
Health, Graduate School of Medicine, The
University of Tokyo
Representatives of Supporting Agencies:
Mr. Kenji Okayama, Director, Office of Guidanceand Investigation, General Affairs Division,
Health Service Bureau, Ministry of Health,Labour and Welfare (MHLW)
Dr. Kaoru Manabe, Deputy Director, General Affairs
Division, Health Service Bureau, MHLW
Dr. Yukako Hinohara, Deputy Director, General
Affairs Division, Health Service Bureau, MHLW
Mr. Kazuhiro Kanayama, Deputy Director, General
Affairs Division, Health Service Bureau, MHLW
Mr. Glenn S. Podonsky, Chief Health, Safety andSecurity Officer, Office of the Secretary ofEnergy, U.S. Department of Energy (DOE)
Dr. Patricia R. Worthington, Director, Office of
Health and Safety, Office of Health, Safety andSecurity, DOE
Mr. Dean C. Hickman, Program Manager, Officeof Health, Safety and Security, DOE
Dr. Joseph F. Weiss, Japan Program Manager, Officeof International Health Studies, Office of Health,
Safety and Security, DOE
Mr. Ronald C. Cherry, Energy Attaché and Director,
DOE Tokyo OfficeDr. Warren R. Muir, Executive Director, Division
on Earth and Life Studies, National ResearchCouncil (NRC), National Academy of Sciences(NAS)
Dr. Kevin D. Crowley, Director, Nuclear andRadiation Studies Board, Division on Earth andLife Studies, NRC, NAS

Participants of the 44th Board of Directors Meeting

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RERF Update Volume 20, Issue 2, 2009

RERF News
Dr. Daniela Stricklin, Program Officer, Nuclear andRadiation Studies Board, Division on Earth andLife Studies, NRC, NAS

4
Dr. Evan B. Douple, Associate Chief of Research
Dr. Nori Nakamura, Chief Scientist
Dr. Kazunori Kodama, Chief Scientist
Mr. Douglas C. Solvie, Associate Chief of Secretariat

RERF:
Mr. Eiji Akimoto, Chief of Secretariat

As of 17 June, 2009, Susan M. Geyer resigned
as an Associate Senior Scientist in the Departmentof Statistics. Dr. Geyer returned to the U.S. where
she accepted a position of Associate Professor in
the Department of Internal Medicine in the Ohio
State University College of Medicine, and Senior
Biostatistical Scientist in the university’s Center for
Biostatistics. Drs. Jun-ichi Asakawa, Fumiyoshi
Kasagi, and Kiyohiro Hamatani reached mandatory
retirement age on 30 June 2009 and were re-employed
1 July 2009 as Fixed-term Research Scientists in the
Departments of Genetics, Epidemiology, andRadiobiology/Molecular Epidemiology, respectively.
Dr. Nobuo Nishi, Assistant Chief in the Departmentof Epidemiology, resigned effective 30 September
2009 and took a position of Project Leader, Centerfor Collaboration and Partnership at the National
Institute of Health and Nutrition.
Dr. N. Pillip Ross resigned as Chief, Departmentof Statistics, effective 13 October 2009. Dr. Harry
M. Cullings, former Assistant Department Chief,
was promoted to Acting Department Chief effective
14 October 2009. Dr. Norio Takahashi wasre-employed with the title of Fixed-term Research
Scientist in the Laboratory of Biochemical Genetics
effective 1 November 2009.
Dr. Ritsu Sakata, Research Scientist in the
Department of Epidemiology, spent eight months as
a visiting scientist at the U.S. National Cancer
Institute. We have asked her to write a little about
her experience.
Finally, Dr. Kanya Hamasaki was appointed asa Fixed-term Research Scientist in the Departmentof Genetics effective 1 September 2009. We also haveasked Dr. Hamasaki to write a little about himself
and his interest in the work of RERF (see also his
scientific article on page 14).
Ritsu Sakata
I am very appreciative that I was given an
opportunity to study at the Radiation Epidemiology
Branch of the U.S. National Cancer Institute (NCI)
for the eight-month period between December 2008
and August 2009. At the Radiation Epidemiology
Branch, Drs. Kiyohiko Mabuchi, Charles Land,
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and Elaine Ron, who havevisited RERF many times,
helped me in many ways tomake me feel comfortable
during my stay. Under
the direction of Dr. Peter
Inskip, I was mainly involved in a reanalysis ofmortality data on women
undergoing radiation treatRitsu Sakata,
Research Scientist
ment for benign gynecological diseases and am
currently putting the finishing touches on a related
manuscript.
NCI had in its basement a gym complete withshowers, and many people used the facility at times
when they were off from work. I joined a runningteam and often jogged through the lush residential
area neighboring NCI during my lunch breaks. Afterrunning, I would take a shower and resume myafternoon work schedule feeling quite refreshed.
In addition to this, since the quantity of meat andprepared dishes sold at the supermarket andrestaurants was all too much for me living alone, I
took to cooking my own food centered on vegetables,
and this led a very health lifestyle while I was there.
Thanks to that lifestyle, and maybe counter to the
expectations of some of my colleagues, I did not gain
any weight in the U.S., and my body fat ratio actually
decreased. Back in Japan, I now feel as if I am
somewhat lacking sufficient exercise.
The start of my life in the U.S. was initially helpedby Dr. Kyoji Furukawa, who had already been in the
country for seven months by the time I arrived. When
preparing to return to Japan, I was helped by the many
new friends I made while in the U.S. Even though
my stay was short, I was able to accomplish a lot,
experienced differences in life and work between the
U.S. and Japan, and made many good friends. I closeby thanking all those who helped make that valuable
experience possible.
Kanya Hamasaki
Although I arrived at RERF in April of 2001 andhad been working as a technician in the Department
RERF Update Volume 20, Issue 2, 2009

5

RERF Newsof Radiobiology/Molecular
Epidemiology, I was especially pleased to be employed as a Fixed-term
Research Scientist in the
Cytogenetics Laboratory of
the Genetics Department,on 1 September 2009. In
2003, I began studies in
Kanya Hamasaki,
the Graduate School of
Research Scientist
Biomedical Sciences at
Hiroshima University while
continuing to work at RERF. I completed andreceived the PhD in May 2009. The thesis of mydegree was “Clonally expanded T lymphocytes from

A-bomb survivors in vitro show no evidence of cytogenetic instability.”
I would like to express my appreciation to everyone who helped me accomplish my goals, especiallymembers of the Departments of Genetics andRadiobiology/Molecular Epidemiology. My current
and future work is based on the cytogenetic techniques that I learned at RERF. I am going to participate in the projects “biological dosimetry study” and“chromosome studies in the in utero-exposed population.” It is my great pleasure to face the challenges
ahead, such as resolving issues that remain unclear.
I hope to make a contribution to the many great
achievements of RERF.

Visiting Scientists
While several scientists visit RERF throughout
any given year, some scientists stay for several days
or weeks and others stay for several months tocollaborate with RERF researchers. On July 27 and28, Dr. Timothy E. O’Brien, Associate Professor
and Graduate Program Director of the Departmentof Mathematics and Statistics at Loyola Universityof Chicago, U.S., visited RERF and presented a seriesof lectures on “Applied Nonlinear Statistical
Methods.” Dr. O’Brien teaches a similar short-course
on a regular basis in the U.S. under the auspices of
the American Statistical Association. He pointed out
in his lectures that while researchers often recognizethat nonlinear regression models are often more
applicable for modeling physical and medical
processes than are linear ones, selecting an efficientexperimental design, choosing, fitting, and interpreting an appropriate nonlinear model, and deriving
and interpreting confidence intervals for key model
parameters can present fundamental and important
challenges. The course was well attended, including
some researchers from Japanese universities.
This fall we were fortunate to have a former RERF
Chief of Epidemiology, Dr. Kiyohiko Mabuchi,
currently a scientist in the Radiation Epidemiology
Branch of the U.S. National Cancer Institute (NCI),
spend some time working on matters related to the
RERF Contract with the NCI. In addition, a former
Chief of Statistics, Dr. Dale Preston, HiroSoft Chief
Scientist, and a former Senior Research Scientist,
Dr. Donald Pierce, were also at RERF collaborating
on a number of studies and providing consultation.

Visiting Student Researchers
Throughout the year there are often students fromvarious countries visiting RERF as trainees who learn
experimental techniques and conduct research. They
work closely with RERF research scientists and theirvisit is supported by a number of fellowships or fromtheir home country’s government. During the past
year, two trainees were supported by an award fromthe Hiroshima International Council for Health Careof the Radiation-exposed (HICARE). HICARE’sinternational cooperation activities include the training of medical and other technical personnel involvedin the health care of the radiation-exposed worldwide, the dispatch of medical and other specialists
in Hiroshima to the radiation-exposed countries/
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regions, and dissemination of knowledge about the
medical care of the radiation-exposed people.
From 3 September until 6 November, 2009, Liga
Larmane, from the Liga Stradins University in
Latvia, and Oleg Kovalev, from the Federal
Institution Medical Radiological Research Center(MRRC) of the Russian Academy of Medical
Sciences, received training and conducted research
in RERF’s Department of Radiobiology/Molecular
Epidemiology (RME). Since May 2008, Ms.
Larmane has been working in the university’sLaboratory of Biochemistry and is a student in the
Doctoral Programme in the Faculty of Medicine. She
has been working in the field of oxidative stress and
RERF Update Volume 20, Issue 2, 2009

6

RERF News
antioxidents, studying the effects of long-term
antioxidant therapy in Chernobyl clean-up workers
from Latvia. Her goal at RERF was to learn various
experimental techniques that would be used in her
doctoral thesis and specifically to investigate theeffects of radiation on lymphocyte subset frequencies
and intracellular reactive oxygen species levels in amouse model. Mr. Kovalev is working in the
Department of Radiation Biochemistry at MRRC andhas been conducting genomic instability research.
His goal at RERF was to learn and apply methods ofimmunofluorescent detection of phosphorylated
histone H2AX for studying genomic instability
induced by low doses of radiation. Both trainees havecompleted their program at RERF under the
mentorship of Dr. Tomonori Hayashi, Chief of the
RME’s Immunology Laboratory.

Liga Larmane from Latvia (left) and Oleg Kovalev from
Russia (center) talking with Dr. Akihiko Suyama,
Chief, Nagasaki Epidemiology Department

2009 Distinguished Lecture Series
On 19 June 2009, Dr. Janko Nikolich-Zugich gavea distinguished lecture entitled “T Cell Function andHomeostasis in Immune Senescence: Causes andConsequences.” Dr. Nikolich-Zugich is Chairman of
the Department of Immunobiology, Co-director of
the Arizona Center on Aging, and Elizabeth Bowman

Professor in Medical Research in the College ofMedicine, all at the University of Arizona in Tucson,
U.S. He is a recognized expert in the effects of aging
on the response of the immune system and is acollaborator in the new RERF study on the effectsof radiation on immunosenescence.

Awards Received by RERF Scientists
Upon Receiving the 26th Tsunoo
Scientific Prize
Misa Imaizumi, Chief
Division of Radiology
Department of Clinical Studies, Nagasaki

I recently received, on May 25 of this year, the26th Tsunoo Scientific Prize. Every year, theNagasaki University School of Medicine awards thisprize to a researcher 40 years of age or younger who
has made important scientific contributions to thefield of medicine in Nagasaki Prefecture, in memoryof the great achievements of the late Dr. Susumu
Tsunoo, who contributed greatly to the developmentof Nagasaki Medical College. During his term aspresident of the college, Dr. Tsunoo was exposed tothe atomic bomb on August 9, 1945, while he wasworking at an outpatient clinic, and passed away at
the young age of 52. Receiving this prize, I newly
confirmed my determination to continue studies on
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health effects in the A-bomb survivors.
The prize-winning research was “Study on
Thyroid Diseases among A-bomb Survivors,” which
was conducted with cooperation from subjects of the
Adult Health Study. During the period from 2000 to
2003, we jointly conducted thyroid examinations in
Hiroshima and Nagasaki for the first time, and foundthat prevalence of not only malignant thyroid tumors,
but also benign nodules, were related to radiation
dose. Our study also showed that the younger theage at exposure, the greater the effects were ofradiation exposure. On the other hand, no significant
relationship between radiation dose and thyroid
nodules was observed among survivors exposed inutero, although their risk ratio was similar to thatamong those exposed at a young age. The results
showed effects of A-bomb radiation on thyroid
nodules among those surviving 50 years or more after
exposure.
In 2000, this research was initiated under theleadership of Drs. Tan Tominaga and Toshiro Usa,
RERF Update Volume 20, Issue 2, 2009

RERF News

Misa Imaizumi, Research Scientist, next to the statueof Dr. Susumu Tsunoo

my predecessors and, in 2001, I took over the
project as the responsible researcher. At first, I was
overwhelmed by the work and grew worried for atime, but many people in not only the Departmentsof Clinical Studies in Hiroshima and Nagasaki but
also elsewhere, including the Departments ofStatistics, Epidemiology, and Information Technology,
made concerted efforts together to promote the study.
While conducting this research, I have learned a greatdeal, including not only about the techniques andorganizational resources that RERF has accumulated
over the years, but also about its scientists’ sincere
attitudes toward research, contributions to the
A-bomb survivors, and sense of mission. I now
realize how wonderful it is to be able to engage insuch valuable research at RERF. In the future, I would
like to continue my efforts involving thyroid researchin particular. Everyone’s guidance and support would
be truly appreciated.

Upon Receiving Education Award fromthe Hiroshima University Departmentof Molecular Internal Medicine
Yoshimi Tatsukawa, Research Scientist
Department of Clinical Studies, Hiroshima

I recently received an Education Award from the
Department of Molecular and Internal Medicine(former Second Department of Internal Medicine),
Hiroshima University. This prize is awarded to those
who belong to that department for their achievements
at universities or research institutes (excluding
related hospitals).
In 1998, I obtained a medical license and, 10 years
later (last year), received a doctoral degree based on
the thesis for which I received the aforementioned
Education Award. Looking back on the past 10 years,
I feel strongly that I was able to have such successthanks to the support of many people. I gave birth tomy first child just before finishing my two-year
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7internship as a physician. Because there was notmuch acceptance of a female physician working in aclinical setting while raising a child, I almost gaveup the idea of working as a clinician. A doctor in
the university medical office, however, offered
warm words of encouragement, asking whether I
would be interested in joining the Second Department
of Internal Medicine and working as a clinician after
giving birth to my child. I therefore joined thedepartment, and worked at related hospitals as aclinician for four years.
While I lived a busy life, examining patients andraising a child, I wondered whether to quit working
as a clinician and pursue research instead. Physiciansat the hospital where I worked encouraged me byadvising me that, “You can work as a clinician at
any time, but if you want to start research, you better
do it while you are young.” Another doctor of theuniversity medical office invited me to attend
university meetings to read and discuss papers, andI quickly accepted the doctor’s call to participate.
This eventually led to the opportunity for me to work
at RERF. The paper for which I received the award
was based on my first study at RERF. I feel that the
Education Award has provided me a helping handby reminding me that getting a degree is a beginning
not an end.
Finally, I would like to express my sincere appreciation to the doctors in the medical office andrelated hospitals
who have guided
me along the way,
and to all the staff
at RERF, and themembers of myfamily, who havealways supported
me. I hope to beable to continue
and further myown work, and tothat end, everyone’s continued
instruction and Yoshimi Tatsukawa, Researchguidance would be Scientist, with her award
truly appreciated.

Excellent Poster Award Received fromthe Japanese Association of Cancer
Registries
Hiromi Sugiyama, Research Scientist
Department of Epidemiology, Hiroshima

At the 18th general assembly/workshop of theJapanese Association of Cancer Registries (JACR),
held on September 3 and 4, 2009, in Niigata
RERF Update Volume 20, Issue 2, 2009

RERF News
Prefecture, my poster presentation titled “Cancer
incidence in Hiroshima Prefecture” won the award
for excellence in the academic poster category. In
the category introducing regional cancer registry
offices, both prefectures of Hiroshima and Nagasaki
also won awards (with material prepared by the
Tumor and Tissue Registry Office, Department of
Epidemiology, Nagasaki Laboratory), doubling thejoy experienced by those concerned.
There are currently three cancer registry projects
ongoing in Hiroshima Prefecture: the Hiroshima City
Cancer Registry, the Hiroshima Prefecture Tumor
Registry (a tissue registry), and the Hiroshima
Prefecture Cancer Registry. A data-sharing agreement starting on August 1, 2009, was signed among
the three projects, thereby allowing compilation ofdetailed incidence statistics covering the entire
Hiroshima Prefecture based on information fromabstracted records and pathological diagnoses,
among other sources. For example, Hiroshima
Prefecture has thus far observed high mortality fromliver cancer and also recently found higher livercancer incidence, compared with national levels. I
hope to elucidate the background of cancer incidence
in Hiroshima Prefecture by further analyzing theprefecture’s cancer incidence trends, with the aim ofunderstanding cancer incidence among A-bomb
survivors.
My award-winning poster was selected in a votecast by all participants of the general assembly/
workshop, including a significant number of administrative personnel and cancer registry operators
as well as researchers, and hence the decision apparently was dependent on visual impact rather thanmerely content. Speaking of poster presentations,visual impact is considerably important. Wheneverpreparing a poster, I keep in mind the following
simple tips: 1) Text should be legible from overone meter away; 2) Results should be shown in
the form of two-dimensional graphs if possible (thecomplexity of three-dimensional graphs may limit
the efficient transfer of information); 3) Choiceof colors should beconsidered carefully(red and green shouldbe employed only
sparingly together);and 4) A single sentence/phrase of key
information should
be shown alongside
graphs. Getting ahandle on these tips
will greatly improve
poster visuals. In the
future, I hope to fur- Hiromi Sugiyama, Researchther develop my re- Scientist, with her poster
search activities and award
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8
refine my presentation skills. Your continued support and advice to that end would be greatly appreciated.

Dementia Study Presented ASAD Best
Scientist Award and Published in
World Federation of Neurology
Newsletter
Michiko Yamada, Assistant Chief
Department of Clinical Studies, Hiroshima

I recently received the Best Scientist Award at
the 3rd International Congress of the Asian Society
Against Dementia (ASAD), held in Seoul October
11–13, 2009. I have been studying cognitive function,
incidence, risk factors, and complications/prognosis
in terms of dementia for the dementia study that was
initiated by RERF in 1992 based on research protocol(RP) 5-92 “Study of senile dementia among the Adult
Health Study,” in long-term collaboration withmembers of the Departments of Clinical Studies,
Epidemiology, Statistics, and Information Technology. As guidance from dementia experts is essential
for this study, we engage in collaboration withspecialists at Hiroshima International University,
the Department of Clinical Neuroscience andTherapeutics of Hiroshima University, and physicians practicing at medical institutes in Hiroshima.
The award was granted to our study titled “Reaction time as a predictor of mortality and dementia.”
Reaction time was measured in 1970–72 as one ofseveral physiological functions investigated todetermine whether atomic-bomb radiation accelerated aging. I reported that reaction time was related
to subsequent mortality and dementia development,
and that risks of mortality and dementia were higher
for those with slow reaction time in mid-adulthood.
During the recent meeting, I was able to learn
about progress being made in dementia research in
Asian countries,
and also obtained
the latest information on basic
research, diagnostic imaging,and treatment of
Alzheimer’s disease in Europe
and the UnitedStates.
The study subjects of RP 5-92
are AHS participants at least 13 Best Scientist Award presented
years of age at from the Asian Society Against
the time of bomb- Dementia
RERF Update Volume 20, Issue 2, 2009

RERF News
ings. Analysis results to date have not shown any
indication of radiation-associated impairment ofcognitive function or increased dementia incidence.
A paper based on this finding titled “Incidence of
dementia among atomic bomb survivors—Radiation
Effects Research Foundation Adult Health Study”
was published in the Journal of the Neurological Sciences in March 2009, and was introduced in theNewsletter of the World Federation of Neurology thispast October.
I am truly grateful for the opportunities provided
me to be involved in such important research taking
place at RERF. Everyone’s continued support would
be greatly appreciated.

Receiving the MEXT 2009 Minister’sAward—Distinguished Service for
Nuclear Safety Management
Kazuo Neriishi, Assistant Chief
Department of Clinical Studies, Hiroshima

The awarding ceremony for the 2009 Minister’sAward—Distinguished Service for Nuclear Safety
Management—was held on November 6, 2009,at the Tokai University Club, located in the
Kasumigaseki Building in Tokyo, where certificatesand plaques from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT) were
distributed to 17 awardees, including myself, by Vice
Minister Masaharu Nakagawa. The selection
committee indicated that I had received the honor
because I have worked on health examinations
conducted among area residents after the JCO
criticality accident occurred in the village ofTokaimura on September 30, 1999, and participatedin the subsequent health examinations starting in2000 and conducted every April since on a regularbasis. Taking this opportunity, I would like to express
what I have felt strongly throughout my experiences.
First of all, I would like to pray for the souls of
the two victims of the accident and express mycondolences to their families. After the accident, thenational government embarked on interministerial
arrangements for prevention of such disasters, andan appropriate structure has been completed to acertain extent. I do not, however, believe the current
situation is satisfactory. From the viewpoint of aradiation researcher, I strongly feel that a majority

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9of the general public, including the media and thegovernment, misunderstand effects of radiation onhuman health and that more accurate informationneeds to be conveyed to the public. Such dissemination of accurate knowledge within government
policies alone would resolve several issues. For
example, radiation affects human health in the formof increased numbers of such common diseases ascancer among those exposed to radiation, comparedto the non-exposed. Lacking appropriate relativerisk information, however, people may worry
unnecessarily about long-term heath problems,
occasionally leading to serious societal crises.
In consideration of this point, I have worked on
both physical and mental health management for suchindividual residents. I have learned through theactivities that I should not be so hasty to convince
those who are worried about health effects ofradiation otherwise. Instead it is important to besomeone with whom they can discuss problems
or questions at any time. In this regard, I think workof this nature contributed to my receiving the
aforementioned honor.
What approaches can be adopted for the purposeof dissemination of accurate information? I hereby
propose the establishment of a training system
under which new findings obtained by RERF can bedirectly reflected in government policies. Every year
RERF generates a number of new findings, rapidly
updating the existing body of knowledge. I make this
proposal because at least 10 years are now required
for the national government to ratify internationalradiation standards that provide the government with
scientific grounds
for revision. Furthermore, it is necessary
to establish a framework under which any
information newly
acquired by the government is continuously provided to
citizens.
In closing, I would
like to extend myheartfelt appreciation
to the many people Kazuo Neriishi, Assistant
who supported me in Depar tment Chief, withthe work for which I MEXT award plaque andcertificate
received this award.

RERF Update Volume 20, Issue 2, 2009

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Conference and Workshop Reports

Late Health Effects of Ionizing Radiation: Bridging the Experimental
and Epidemiologic Divide
Evan B. Douple, Associate Chief of Research
Despite the threat imposed by an H1N1 influenza
outbreak, RERF was well represented by a delegationof six scientists at a conference held at theGeorgetown University Conference Center on thehistoric campus in Washington, DC, May 4–6, 2009.
Planned by an organizing committee that included
RERF Vice Chairman and Chief of Research Roy
Shore, the multidisciplinary conference focused on
emerging data and new challenges in radiation
sciences, with the aim to stimulate collaboration andsynergistic interactions among the approximately 150
participants. There were 12 scientific sessions witha total of 36 invited speakers from the fields ofradiobiolgy, dosimetry, epidemiology, and statistics
on topics ranging from experimental biology toepidemiologic studies of radiation-exposed
populations. The papers from all invited speakers,
including RERF’s Kyoji Furukawa (Interaction
Effects of Radiation and Smoking on Lung Cancer
Risks among Atomic Bomb Survivors), Yoichiro
Kusunoki (Immunological Alterations in Aging
A-bomb Survivors), and Roy Shore (Cataract Risk
at Low-to-Moderate Radiation Doses: (Not) Seeing
is Believing), will be published in a supplement of
the journal Radiation Research. The conference wassponsored by the U.S. National Cancer Institute(NCI), Georgetown University Medical Center,
Helmholtz Zentrum Munchen, the U.S. National
Institute of Allergy and Infectious Diseases, and the
U.S. Environmental Protection Agency.
Two poster sessions were included with a totalof 100 posters covering a diversity of issues including effects of radiation quality, mechanistic modeling, non-targeted effects, genomic instability,
biodosimetry, dose reconstruction, dose uncertainties, medical radiation and germline mutations,
thyroid cancer in French Polynesia and Chernobyl,lung cancer and radiation/smoking interactions,radiation and cognitive disorders, radiation doses tointerventional medical practitioners, and many otherinteresting topics. RERF’s Nobuo Nishi andcolleagues had a poster on “A New Mail Survey on
the Life Span Study (LSS) Cohort” and Ritsu Sakata
and her colleagues presented a poster “Effects of
Other Factors in Radiation Risk Assessment of
Gynecologic Cancer Incidence.” Harry Cullingsand colleagues presented a poster on “EstimatedGamma Doses to the Teeth of the Japanese Atomic
Bomb Survivors.” Former RERF Visiting Scientist,
David Richardson (University of North Carolina)presented his work in collaboration with RERF
Return to Table of Contentsscientists, “Ionizing Radiation and Leukemia
Mortality among Japanese Atomic Bomb Survivors,
1950–2000.”
The conference began with a comprehensive
review of some of the evidence for key biologicalevents that may play an important role in radiation
health effects such as the bystander effect. Resultsfrom microbeam experiments and the contributionsof studies using cultured cells, 3-D models such as
tissue explants, and in vivo studies were described.
Additional speakers described the challenge ofattempting to account for such radiation-induced
effects as genomic instability, bystander effects, or
low-dose hypersensitivity in cancer epidemiology.
Ohtsura Niwa (National Institute of Radiological
Sciences, Chiba, and RERF Scientific Councilor)
described stem cell radiobiology and provided
evidence that the stem cells are a likely target for
initiating some solid cancers.
The morning of the second day of the conference
focused on quantifying the carcinogenic effects inradiation workers, including lymphohematopoietic
malignancies and thyroid cancer in Chernobyl cleanup workers, mortality and cancer incidence following
occupational radiation exposure in the third analysisof the U.K. National Registry for Radiation Workers,
joint effects of radon exposure and smoking on lungcancer risk among uranium miners, cancer risks inmedical radiation workers, updated results of theGerman uranium-miner cohort study (radon and therisk of lung and non-lung cancer), and results of asecond follow-up of cancer mortality among German
aircrew.
The afternoon session focused on site-specificcancers following environmental exposures. Former
RERF Chief of Statistics, Dale Preston (HiroSoft
International Corporation), pointed out that theextreme variability in the site-specific risk estimates
based on studies of Mayak workers and people who
lived along the Techa River is largely a consequenceof the small number of excess cases. RERF’s Kyoji
Furukawa reported the results of studies of the joint
effects of smoking and radiation on lung cancer risks
in the LSS cohort of the A-bomb survivors. He
concluded that the interaction between smoking andradiation results in an excess relative risk (ERR)
that decreases with increasing age and is supermultiplicative for light smokers but additive or
sub-additive for heavy smokers.
The third day included a focus on the late healtheffects of radiation therapy, and on radiation-related
RERF Update Volume 20, Issue 2, 2009

Conference and Workshop Reports

11

non-malignant conditions such as cardiovasculardisease, cataracts, and non-malignant thyroid
diseases. A session on radiation exposure and nonmalignant conditions included Yoichiro Kusunoki’s
review (presented by Evan Douple) of the RERF
studies of the effects of radiation on the immune
system of A-bomb survivors in which many effects
are similar to the normal immunosenescence seen inaging populations. In addition, RERF’s results
suggest that increases in plasma levels of inflammatory cytokines with increased radiation dose
support the hypothesis that T-cell immunologicalalterations linked to an enhanced inflammatory
response may lead to the development of inflammation-related diseases such as cardiovasculardisease in the A-bomb survivors. Roy Shore
described the latest evidence from RERF studies ofradiation-induced cataractogenesis in which a clear
dose-response is seen for cataract surgery incidence
and with a suggestion that the dose threshold may
be lower than previously thought. Those results,
coupled with similar observations in other studies,
have instigated reassessments of the guidelines for
exposure of the lens of the eye by various radiation
protection bodies.
The final session included two keynote lectures.
The first by David Brenner (Columbia University,
New York) reviewed the risks and benefits associatedwith the rapidly growing use of one of medicine’s
higher radiation dose procedures, the CT scan. The
annual number of CT scans is rapidly increasing inJapan and the U.S. (approximately 70 million in the
U.S.; Japan leads the world in numbers of CT scansper capita), CT scans are now producing about halfof the annual radiation exposure from medical
procedures, and many of the scans include pediatricpatients. He concluded that while CT risks are small,a small risk multiplied by many millions of scansmight translate into a public-health concern someyears in the future, particularly from pediatric CTs.

The second keynote lecture, by Julian Preston (U.S.
Environmental Protection Agency), focused onradiation risk perception, communication, and policy.
He reminded the audience that there are really two
bridges to cross; the first is from the environmental
observations to epidemiology, while the second isbridging the gap from science to risk management
and to the public. It is very difficult to put risks inproper perspective because any number projecting
adverse health effects, regardless of how small, islikely to be viewed as unacceptable by a public thatis generally risk averse and favoring “zero risk”
which is often unrealistic, expensive, or unattainable.
The conference concluded with observations bya panel of experts, including RERF’s Roy Shore.
The panelists were asked to select their two mostimportant “gaps of information” that they felt should
be a focus for future research and needed to be filled.
New techniques for cancer therapy, such as intensitymodulated radiation therapy (IMRT; delivering theradiation so that the beam enters the body from manydifferent angles to get to the tumor with pinpoint
accuracy) and stereotactic radiation surgery (SRS;
destroying diseased tissue with an intense, highlyfocused beam) are changing the way radiation
therapy is applied and will involve large radiation
doses delivered in small numbers of treatments withsome scatter of radiation to normal tissues. Other
panelists (a) encouraged development of bettermodels for estimating doses, including models that
actually work and that will integrate internal andexternal doses, (b) called for improved biodosimetry
and methods for pooling data, (c) suggested a focus
on certain tumors for which radiation-associated risks
have not been well characterized such as cancers of
the GI tract, and (d) improved biomarkers andbiologically-based dose response models.
The continuous rainy weather throughout theconference did not dampen the spirits of the six
RERF scientists who felt they received important

Dr. Kyoji Furukawa presenting his paper on interaction effects of radiation and smoking on lung cancer
risk

Dr. Ritsu Sakata explaining her poster on ERRs
with adjustment for factors possibly associated withgynecologic cancer

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RERF Update Volume 20, Issue 2, 2009

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Conference and Workshop Reports
information regarding the status of the radiation
epidemiologic studies of some of the world’s majorradiation-exposed cohorts. This was an especially
important conference for RERF’s Chief of Epidemiology, Kotaro Ozasa, whose first visit to
Washington, DC, included valuable discussions with
the international radiation scientists and a visit to
the Radiation Epidemiology Branch of the U.S. NCI
in Rockville, Maryland. While some of the study
cohorts described are impressively large (suchas 240,000 Chernobyl “liquidators,” 116,000“evacuees” from the Chernobyl area, and 5,000,000
exposed to <555 KBq/m2 of Cs-137 from Chernobyl),most studies are plagued by one or more limiting

factors such as large dosimetric uncertainties,
healthy-worker effects, relatively short follow-up,
low mean radiation doses, confounding factors(known and unknown), and small numbers of excess
cases. We were all reminded on several occasions
during the conference of the continued importanceof, and interest in, the results of the studies underway
at RERF. It was clear that there is a strong needfor improved biophysical and mechanistic
understandings before scientists are able to bridge
the gap between basic science and epidemiology—
and that there is great potential benefit if mankind isable to do so.

Dose Uncertainty Workshop
Harry M. Cullings, Acting Chief
Department of Statistics
A one-day workshop was held on May 8, 2009,at the Georgetown University Conference Center in
Washington, DC, entitled “Impact of Uncertainty in
Dose to the Dose Response.” The workshop wasorganized by Dr. Andre Bouville of the Radiation
Epidemiology Branch of the National Cancer
Institute (NCI). The workshop was held inconjunction with the “Late Health Effects of Ionizing
Radiation Conference” previously described. The
purpose of the workshop as defined by the organizers
was “to explore how uncertainties in individual dose
estimates affect the statistical power and shape ofthe dose response in epidemiologic investigations
and to review strategies that are in use today to try
and account for the impacts of dose uncertainty.”
The workshop was a successor to a similar one heldin 1997 by NCI.
The workshop began with a statement of the
problem from the points of view of a dosimetrist,a statistician, and an epidemiologist. The lastperspective was presented by RERF’s Vice Chairman

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and Chief of Research, Roy Shore. Three casestudies were examined of major populations exposed
to ionizing radiation: the A-bomb survivors; thechildren exposed to I-131 fallout from the Chernobyl
accident; and the people of Kazakhstan exposed to
the fallout from the nuclear tests conducted there.
Each case study had three presentations including:(1) quantification and organization of the uncertainties; (2) assessment of the dose response; and(3) possible improvements. RERF’s (then) AssistantChief of Statistics, Harry Cullings, spoke on thequantification and organization of dose uncertainties
for the A-bomb survivors. Eight of the program
speakers were scientists who formerly spent timeworking at RERF. The program concluded with apanel discussion led by an eminent Bayesianstatistician from Johns Hopkins University, TomLouis. Owen Hoffman of SENES/Oak Ridge has
been working with Dr. Bouville to document thediscussions and a consensus paper is expected.

RERF Update Volume 20, Issue 2, 2009

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Conference and Workshop Reports

International Symposium Based on Radiation Research Partnership
Kotaro Ozasa, Chief
Department of Epidemiology, Hiroshima
An international symposium based on the
Radiation Research Partnership was held on
September 14–15, 2009. With the objectives ofencouraging radiation health effects research
conducted by young researchers in the areas of
epidemiology and statistics and promoting personnel
exchange, the University of Washington (UW),
Kurume University Biostatistics Center, and RERF
have been carrying out the partnership program
since 2006. The theme of this symposium was“Confounding and modification of radiation effects
by lifestyle and other factors/utilization of mailsurvey data.” The symposium was held with thesupport of RERF’s International Exchange Program,and its objectives were to present summary reportsof relevant studies and to review future research
directions. On the morning of September 14,
Kazunori Kodama (Chief Scientist, RERF), Scott
Davis (Professor, UW), and Tatsuyuki Kakuma(Professor, Kurume University) presented summaries
and future challenges of the partnership programfrom their perspectives. Their presentations were
followed by keynote speeches by Dr. Davis, Kenneth
Kopecky (Professor, UW), and Dr. Kakuma fromtheir theoretical/methodological viewpoints
regarding the symposium theme.
In the afternoon of the same day, symposium
participants made presentations on studies ofradiation-related cancer risks, as follows:• study on bladder cancer by Eric Grant(Associate Senior Scientist, Department of
Epidemiology, RERF);• two studies on second primary cancers by
Nobuo Nishi (Assistant Chief, Department of

Epidemiology, RERF) and Christopher Li(Research Assistant Professor, UW);
• studies on colon cancer and breast cancer by
Erin Semmens and Jean McDougall (PhD
students, UW);
• study on dose-response risk model by
Yoshisuke Nonaka (Visiting Research Fellow
at the Department of Epidemiology from
Kurume University); and• study on causal models by Wan-Ling Hsu(Research Scientist, Department of Statistics,
RERF).
Papers reporting the results of these studies arescheduled to be published in the future.
On September 15, active discussions were held
on future perspectives of research based on thesummaries presented on day 1. As a part of a personnel exchange program with Kurume University, Ritsu
Sakata was hired as a research scientist by the
Department of Epidemiology in Hiroshima, and Dr.
Nonaka is currently engaged in his research work as
a visiting research fellow at the Department of
Epidemiology in Hiroshima. Partnership activities
are ongoing. From UW, the above-mentioned two
PhD students and other researchers have produced
research results on radiation health effects based on
RERF data. The UW members also said that, in
addition to using RERF data, they had an opportunity
to feel what the A-bombed city of Hiroshima has
experienced through their stay at the Hiroshima
Laboratory as a part of the exchange program. RERF
research staff members have regularly visited UW
to conduct research discussions, and Mr. Grant has
had an opportunity to study epidemiology as a PhD
student at UW. The three organizations
agreed that it would be worthwhile to try
to obtain research funding to continue thepartnership program. It was noted that
one example of collaborative projects tobe promoted would be to analyze
confounding and modification ofradiation health effects by lifestyle andother factors based on informationcollected from past mail surveys, which
was also a theme of this symposium.
RERF needs to make systematic analyses
in this area of research, which will beappropriate training of PhD students.
Further development of the partnershipprogram is eagerly anticipated.
Participants of the international symposium based on Radiation
Research Partnership held at Hiroshima Laboratory

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RERF Update Volume 20, Issue 2, 2009

14

Science Article

Chromosome Instability in Peripheral Blood T
Lymphocytes from A-bomb Survivors—In Vivoand In Vitro Studies*
Kanya Hamasaki and Yoshiaki Kodama
Department of Genetics, Radiation Effects Research Foundation (RERF)*This article is based on the following publications:Ref. 1. Kodama Y, Ohtaki K, Nakano M, Hamasaki K, Awa AA, Lagarde F, Nakamura N. Clonallyexpanded T-cell populations in atomic bomb survivors do not show excess levels ofchromosome instability. Radiat Res 164:618–26, 2005.
Ref. 2. Hamasaki K, Kusunoki Y, Nakashima E, Takahashi N, Nakachi K, Nakamura N, Kodama
Y. Clonally expanded T lymphocytes from atomic bomb survivors in vitro show noevidence of cytogenetic instability. Radiat Res 172:234–43, 2009.

INTRODUCTION
In 1992, Kadhim et al.3 reported that elevatedlevels of non-clonal de novo chromosome aberrations(mainly chromatid-type aberrations) occur in in vitro
culture of mouse hematopoietic stem cells many
generations after exposure to α particles in vivo. This
event was defined as radiation-induced delayed
genomic instability, which is distinguishable fromthe immediate effects of radiation. Many biologists
have considered that such instability may play animportant role in radiation carcinogenesis. It is now
recognized that instability can be studied by not only
chromosome alterations as a marker but also by otherend points such as gene mutations and cell death.4–8
While there are many reports using cultured cells in
vitro or mouse cells in vivo, few studies on genomic
instability have been done with normal human cells.
In fact, it remains to clarify whether chromosome
instability occurs in vivo in humans, especially in
A-bomb survivors who were exposed to radiation
many years ago.
In the Cytogenetics Laboratory (Department of
Genetics, RERF), we have continued the efforts to
examine the frequency of chromosomal aberrationsin the lymphocytes of A-bomb survivors in order toeither validate, or demonstrate biases in, theindividual radiation dose estimates made by physicalmeasurements. In this study, the stable type
chromosome aberrations, such as translocations andinversions were examined, because unstable typeaberrations, such as dicentrics and rings, havedisappeared from the body during the long postirradiation period. The problem for detecting thechromosome instability in A-bomb survivors is that
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there is no good way to distinguish the chromosome
aberrations that were induced immediately after
exposure in 1945 and the aberrations that occurred
later as a result of genomic instability. Two methods
were selected to resolve the issue. One is in vivo
examination using clonal chromosome aberrations
occasionally observed in peripheral blood T
lymphocytes of A-bomb survivors1 and the other isin vitro study using long-term cultured T-lymphocytecolonies obtained from survivors.2
IN VIVO STUDY
Clonal chromosome aberrations
Clonal chromosome aberrations, occasionallyobserved in the lymphocytes of A-bomb survivors,
were defined as the identical aberrations detected in
more than three cells in each blood examination.
Such clonal chromosome aberrations are exclusively
stable-type aberrations, mainly translocations andinversions. It was thought that the clonal aberrations
originated from the stem cells that could survive asevere depletion of hematopoietic stem cells causedby radiation exposure. The frequencies of the cellswith clonal chromosome aberrations were varied
from case to case, up to 50% in the highest case. It
was also reported that such clonal expansions
probably occurred primarily in the first few years
after the exposure.9
If new de novo chromosome aberrations can beshown to appear cell generations after irradiation inclonal cell populations, such aberrations are thought
to be the consequence of genomic instability inthe cell proliferations after irradiation (Figure 1).
Therefore, we have collected the cells with clonal
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Science Article

Figure 1. A lymphoid progenitor cell with a chromosome aberration (mainly translocations)caused by radiation expands clonally in vivo and these clonal cells can comprisea part of the total T-lymphocyte population. Additional subsequent de novotranslocations generated in the clonal cell population are thought to be theconsequence of genomic instability in later cell generations.

chromosome aberrations in the lymphocytes of Abomb survivors and examined the newly induced
chromosome aberrations in those cells.
Materials and Methods
G-band method
Peripheral blood lymphocytes were collected in
the 1980s (41 years after the exposure, on average)from 50 A-bomb survivors whose estimated doses
were more than 1 Gy. Blood samples were obtained
from each of the subjects during periodic healthexaminations (every two years), for a total of three
to six samples. After two days blood culture,
chromosome slides were prepared by conventional
air-drying methods. The total number of metaphases
scored per donor averaged 760 (38,000 cells were
examined in total). Only clones which can be seen
in more than 10 cells were selected for the study.
mFISH method
Three survivors, who are known to carry large
clonal populations from a previous study, were
examined with multicolor FISH (mFISH) analysis(two of the survivor samples overlap with the G-bandstudy subjects). The blood samples were obtained
between 2000 and 2002. After 48 h blood culture,
chromosome slides were prepared by conventional
methods. mFISH was performed with Spectra Vision
DNA probes (Vysis, Downers Grove, IL) according
to the manufacture’s protocol. Acquisition andanalysis of mFISH images was performed using a
CytoVision ChromoFluor System (Applied Imaging,
Newcastle upon Tyne, UK). More than 100 clonalcells were scored for each sample. None of the blood
donors (including the next in vitro study) had a
medical history of cancer before blood drawing.

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Results
G-band analysis
The results showed that 22 clones (952 cells in
total) were detected from 18 survivors with G-band
analysis (Table 1A). The average estimated dose of
the 18 survivors was 2.5 Gy (0.8–3.6 Gy). Following
the careful examination of the 952 cells, we foundseven additional translocations. Since two of seven
were found in the same subject (subject 3) and wereidentical translocations [t(7;14)], we counted thesesubclonal clones as a single event. Thus, thefrequency of newly induced de novo translocations
was 0.6% (6/951).
mFISH analysis
As shown in Table 1B, six clones were detectedfrom three survivors (subjects 2 and 4 overlap with
the G-band study). Eventually, we could observe four
additional translocations in 333 clonal cell
populations with mFISH (1.2%).
Comparison of in vivo data with the frequency of
spontaneous aberrations
In this study, most of the blood samples wereobtained about 40 years after radiation exposure andthe mean age at the examination of the blood donors
was about 61 years old. It was also known that the
spontaneous frequency of translocations in blood
lymphocytes increases with an increase in donor
age.10 Therefore, under the present conditions, itwould be most appropriate to use the translocation
data for unexposed individuals who were about 40
years old for comparison. Since spontaneoustranslocation rates increase with increasing donor
age with upward curvature,10 the increasing level ofbase-line translocation frequency among those of age
40 (irradiated soon after birth) is lower than those of
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Science Article
age 60 (irradiated at about age 20). Thus, we decided
to use our own data with the G-band method which
is based on 181 survivors in our in utero-exposedcohort with estimated doses of <5 mGy,11 because
the mean time span between the radiation exposureand the time when the blood samples were obtained
for the G-band study in 1985 was 41 years. That study
provided a value of 1.2% (219 translocations in a
total of 17,878 cells scored). As shown in Table 1,compared with this spontaneous frequency of 1.2%,
the frequency of additional translocations amongclonal cell descendants was not higher: 0.6% with
the G-band method and 1.2% with the mFISH
method. Thus, chromosome instability with elevatedfrequency of additional translocation by past
radiation exposure was not detected in this study.

IN VITRO STUDY
In the next study, we tried to evaluate the frequency of additional chromosome aberrations inclonally expanding T lymphocytes from A-bomb
survivors with mFISH. This study was intended toprovide information whether long-term in vitro
forced cell proliferation can increase opportunities
to obtain new de novo chromosome aberrations in
culture (Figure 2).
Materials and Methods
Peripheral blood lymphocytes were obtained fromfour female A-bomb survivors. Among them, twowere proximally exposed survivors whose estimateddoses were 1.2 Gy (subject 2) and 2.0 Gy (subject

Table 1. Frequency of additional translocations among in vivo clonal cells examined
Subject
no.a)

Clonal chromosome
aberration

A. G-band analysis1t(3;4)
2t(2;4)
3
4-1
4-2
5
6
7
8
9
10
11-1
11-2
11-3
12
13
14
15
16
17-1
17-2
18

t(2;12)t(4;6),t(5;13)t(1;2),t(2;15)t(X;2)
t(1;6)t(X;1),inv(2)t(2;18)t(X;5)t(X;2)t(6;9)t(X;16)t(14;15)t(10;17),t(20;11)(11;22)t(5;21),t(8;10)t(13;15)t(4;5)t(X;15)t(2;4)
t(1;2),del(5)t(6;10),t(11;17),del(5)Total

B. mFISH analysis2t(2;4)

4-1
4-2
4-3
4-4
19

t(4;6), t(5;13)t(1;2), t(2;15)t(16;20)t(4;8)
inv(1), del(5)Total

No. of clonal cells[fraction of clonalcells (%)]b)

No. of clonal cellswith additionaltranslocationsc)

10 (1.4%)
48 (10%)

0
1
1
2 (1)
1
0
0
0
0
0
0
0
1
0
1
0
0
0
0
0
0
0
0
7 cells (6 events)

336 (14%)62 (5.8%)
10 (0.9%)20 (2.9%)24 (4.0%)
13 (1.8%)
34 (4.0%)
11 (2.0%)
16 (1.8%)
54 (6.3%)
40 (4.7%)
12 (1.4%)
14 (1.8%)
72 (6.1%)
32 (4.4%)
10 (1.1%)
41 (7.0%)
18 (2.5%)
11 (1.5%)
64 (8.8%)952 cells (6.2%)
101 (51%)

65 (12%)31 (5.5%)
26 (4.7%)
10 (1.8%)
100 (38%)
333 cells

1
1
1
0
0
0
0
1
4 cells

Additionaltranslocationst(1;13)t(12;19)t(7;14)t(2;10)t(5;18)t(7;14)0.6%t(1;11)t(1;16)t(1;17)t(1;5;14)
1.2%

a)Subjects with hyphens indicate multiple clones from the same cases.
The fraction of clonal cells is expressed as the number of clonal cells divided by the total
number of cells examined.
c)
Numbers in parentheses indicate the number of events.
t = translocation, inv = inversion, del = deletionb)

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RERF Update Volume 20, Issue 2, 2009

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Science Article

Figure 2. T lymphocytes from A-bomb survivors were clonally expanded in vitro to determine whether chromosome instability can develop during long-term cell culture.

4), respectively. Both are known to carry clonal
chromosome aberrations in vivo with a highfrequency (10–50%), and are overlapped with the invivo study in the previous section. Such clonalaberrations in the two cases were also detected in
the present study (described below). The other two
survivors (subjects 20 and 21, whose estimated doses
are less than 5 mGy) were age- and gender-matched
controls to subjects 2 and 4, respectively.
T-lymphocyte cloning
T-lymphocyte cloning was conducted withconventional methods2 and the cells were cultured
until 106–107 cells were available for chromosome
tests. For subjects 2, 20, and 21, the average culture
time was approximately four weeks, and the numberof population doublings was 23 to 25. In subject 4,
T-cell colonies that had been cloned previously andcryopreserved12 were thawed and cultured in a 24well plate under the same culture conditions.2
mFISH analysis
Chromosome slides were prepared after 2 hcolcemid treatment by conventional air-drying
methods. One hundred cells were scored for eachclone. The mFISH protocol is the same as describedin the in vivo study.
Results
T-lymphocyte clones obtained from A-bomb
survivors
In this study, a total of 66 clones were establishedfrom two highly exposed survivors (subjects 2 and4) and two control individuals (subjects 20 and 21).
Subject 2. Twenty-two clones were obtained
including eight clones with normal karyotype, eightwith the clonal translocations [t(2;4)], five with otherstructural aberrations, and one with an aneuploidkaryotype.
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Subject 4. Fourteen clones were investigated.
They consisted of four clones with normal karyotype,five with the double clonal translocations[t(4;6),t(5;13)], four with other structural aberrations,and one with an aneuploid karyotype.
Subject 20. Twelve clones were obtained, of
which ten clones had a normal karyotypes, one had
a structural aberration, and one had an aneuploidkaryotype.
Subject 21. Of the 18 clones obtained, 14 clones
had a normal karyotype and four had an aneuploidkaryotype.
Since most of the aneuploid clones obtained inthis study involved the X chromosome, and Xchromosome aneuploidy is known to take placecommonly in cultured lymphocytes from elderly
women,13 these clones were categorized as a “normal
karyotype” in Table 2.
Additional chromosome aberrations detected by
mFISH
The types and the numbers of additional
chromosome aberrations detected in each subject aresummarized in Table 2. The results were also shownby the pooled data of exposed and control subjects,
as well as by the difference in karyotype such as
normal, in vivo clone, and other independent
aberrations. As shown in the table, we could detectvarious types of new additional chromosome
aberrations (see Figure 3 for example).
In order to evaluate the effects of A-bomb radiation on the occurrence of chromosome instability,
we performed statistical analyses concerning
the frequency of newly-induced chromosome
aberrations during long-term culture in vitro. It is
well known that mFISH is the most reliable technique
for the detection of exchange-type aberrations suchas translocations (and derivative chromosomes in thisstudy). Thus, the frequency of stable, exchange-type
RERF Update Volume 20, Issue 2, 2009

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Science Article

Table 2. Frequency of additional chromosome aberrations detected in clonally proliferated T lymphocytes in vitro
Subject

Karyotypes

no.
2

4

Total

Additional chromosome aberrations

cells

t

der

dic

dup

del

f

Total

Normalin vivo clone[t(2;4)]
Other aberrations

900
800

7
5

5
3

0
1

0
2

21
18

12
12

45
41

500

3

4

19

0

9

4

39

Total

2,200

15(0.7%)12(0.6%)20(0.9%)2(0.1%)

48(2.2%)

Normalin vivo clone[t(4;6),t(5;13)]
Other aberrations

500
500

1
3

1
6

0
1

2
5

8
12

10
9

22
36

400

1

0

1

2

5

4

13

Total

1,400

5(0.4%)

7(0.5%)

2(0.1%)

9(0.6%)

25(1.8%)23(1.6%)71(5.1%)3,600

20(0.6%)19(0.5%)22(0.6%)11(0.3%)73(2.0%)51(1.4%) 196(5.4%)

1,100
100

3
0

8
0

0
0

3
0

12
2

15
0

41
2

Exposed (subjects 2 + 4)28(1.3%) 125(5.7%)

20

NormalOther aberrations
Total

1,200

3(0.3%)

8(0.7%)

0(0.0%)

3(0.3%)

14(1.2%)15(1.3%)43(3.6%)21

Normal1,800

4(0.2%)

2(0.1%)

2(0.1%)

3(0.2%)

40(2.2%)25(1.4%)76(4.2%)3,000

7(0.2%)

10(0.3%)2(0.1%)

6(0.2%)

54(1.8%)40(1.3%) 119(4.0%)

Control (subjects 20 + 21)

t = translocation, der = derivative chromosome, dic = dicentric chromosome, dup = duplication, del = deletion, f = fragment

aberration (translocation + derivative chromosome;t + der) was used for the statistical evaluation. The
results indicated that the frequency obtained fromthe exposed cases (1.1%, 39/3,600) was greater thanthat of the control (0.6%, 17/3,000), the difference
was not statistically significant, however (P = 0.101)(Table 3). Similarly, no statistical difference wasfound for the total structural aberrations (P = 0.142).
The frequency of additional chromosome
aberrations in “in vivo clonal aberrations” thatshowed the highest frequency of additionalaberrations among three different karyotypes in the

exposed group, was also compared with that of“normal karyotype” populations in control subjects
to examine the effects of the karyotype difference.
As shown in Table 3, the frequency of new
aberrations among the clonal cell populations was
not much different from that in the control individuals(P = 0.114 for t + der and P = 0.130 for total structuralaberrations).
As described above, there was no clear evidence
suggesting the presence of chromosome instabilities
among the clonally expanded lymphocytes in vitro
from A-bomb survivors.

Figure 3. Detection of additional de novo chromosome aberrations with mFISH (Subject 2, in vivo
clone in Table 2). Panel a: Translocation alone, 46,XX,t(2;4). Panel b: Translocation plus nonclonal aberration, 46,XX,t(2;4),der(4)t(4;9). Arrows indicate the translocation between chromosomes 2 and 4 and arrowhead shows the additional aberration (derivative chromosome)involving chromosomes 4 and 9. Two normal intact number 9 chromosomes are evident.

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RERF Update Volume 20, Issue 2, 2009

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Science Article

Table 3. Statistical analyses of the additional chromosome aberration frequencies

Exposed(subjects 2 + 4)
Control(subjects 20 + 21)

In vivo clonalaberrations
Controls (only normal)t + der

Structural aberrations

39/3,600 
(1.1%)

17/3,000 (0.6%)*P = 0.101

196/3,600 (5.4%)
 *P = 0.142

119/3,000 (4.0%)

17/1,300 
(1.3%)
 *P = 0.114
17/2,900 (0.6%)
 *P = 0.130
117/2,900 (4.0%)

77/1,300(5.9%)* Wald test using quasi-likelihood method.

REASONS FOR A LACK OFCHROMOSOME INSTABILITY
As described above, we made an effort to findradiation-induced chromosome instability in thelymphocytes of A-bomb survivors, but no clear
evidence was obtained in both in vivo and in vitro
studies.
Although a number of studies have used humancells and focused on chromosome aberrations as anindex for radiation-induced genomic instability, theresults, both positive and negative, have not always
been concordant.14–26 Such inconsistencies might bedue partly to different genetic backgrounds, ordifferent radiation sensitivities, among individuals.
Considering the polymorphism of individual genetic
factors, the sample size of our present studies (1,300
cells from 19 people for the in vivo study, 6,600 cells
from four persons for the in vitro study) might not
be enough to evaluate the instability. Alternatively,
the results are interpreted to indicate that the
instability, if it exists, is not an event that is frequentenough to be easily detected in the experimental sizethat we used.

Additionally, it is possible that individuals among
the A-bomb survivors who were genetically
predisposed to the induction of radiation-associatedinstability were already eliminated from the
population due to early death from cancer. However,this seems unlikely because cancer risk started toincrease years after the radiation exposure and is still
elevated today, in proportion to the increase in the
background rate.
Since the numbers of studies searching for radiation-induced genomic instability with normal humancells are still insufficient, it is necessary to accumulate data by additional studies. Recently, an increaseof relative risk of myelodysplastic syndrome (MDS)in A-bomb survivors has been reported.27 That reportsuggests a possible involvement of genomic
instability in radiation carcinogenesis in A-bomb
survivors. In that context, further investigation ofradiation-induced chromosome instability inhematopoietic stem cells of A-bomb survivors might
be important. If any findings on genomic instability
could be obtained at the blood stem cell level, theywould serve as new data in terms of development ofradiation-induced instability in vivo.

References
1. 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 instability. Radiat Res 164:61826, 2005.
2. Hamasaki K, Kusunoki Y, Nakashima E, Takahashi N, Nakachi K, Nakamura N, Kodama Y. Clonally expanded
T lymphocytes from atomic bomb survivors in vitro show no evidence of cytogenetic instability. Radiat Res
172:234-43, 2009.
3. Kadhim MA, Macdonald DA, Goodhead DT, Lorimore SA, Marsden SJ, Wright EG. Transmission of chromosomal instability after plutonium alpha-particle irradiation. Nature 355:738-40, 1992.
4. Bedford JS, Dewey WC. Radiation Research Society 1952–2002. Historical and current highlights in radiation
biology: Has anything important been learned by irradiating cells? Radiat Res 158:251-91, 2002.
5. Morgan WF. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic
instability and bystander effects in vitro. Radiat Res 159:567-80. 2003.
6. Morgan WF. Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic
instability and bystander effects in vivo, clastogenic factors and transgenerational effects. Radiat Res 159:581-

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RERF Update Volume 20, Issue 2, 2009

20

Science Article
96, 2003.

7. Wright EG, Coates PJ. Untargeted effects of ionizing radiation: Implications for radiation pathology. Mutat Res
597:119-32, 2006.
8. Ullrich RL, Ponnaiya B. Radiation-induced instability and its relation to radiation carcinogenesis. Int J Radiat
Biol 74:747-54, 1998.
9. Salassidis K, Schmid E, Peter RU, Braselmann H, Bauchinger M. Dicentric and translocation analysis for
retrospective dose estimation in humans exposed to ionizing radiation during the Chernobyl nuclear power
plant accident. Mutat Res 311:39-48, 1994.
10. Sigurdson AJ, Ha M, Hauptmann M, Bhatti P, Sram RJ, Beskid O, Tawn EJ, Whitehouse CA, Lindholm C,
Nakano M, Kodama Y, Nakamura N, Vorobtsova I, Oestreicher U, Stephan G, Yong LC, Bauchinger M, Schmid
E, Chung HW, Darroudi F, Roy L, Voisin P, Barquinero JF, Livingston G, Blakey D, Hayata I, Zhang W, Wang
C, Bennett LM, Littlefield LG, Edwards AA, Kleinerman RA, Tucker JD. International study of factors affecting human chromosome translocations. Mutat Res 652:112-21, 2008.
11. Ohtaki K, Kodama Y, Nakano M, Itoh M, Awa AA, Cologne J, Nakamura N. Human fetuses do not register
chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses. Radiat Res 161:373-9, 2004.
12. Kusunoki Y, Kodama Y, Hirai Y, Kyoizumi S, Nakamura N, Akiyama M. Cytogenetic and immunologic identification of clonal expansion of stem cells into T and B lymphocytes in one atomic-bomb survivor. Blood
86:2106-12, 1995.
13. Fitzgerald PH. A mechanism of X chromosome aneuploidy in lymphocytes of aging women. Humangenetik
28:153-8, 1975.
14. Martins MB, Sabatier L, Ricoul M, Pinton A, Dutrillaux B. Specific chromosome instability induced by heavy
ions: A step towards transformation of human fibroblasts? Mutat Res 285:229-37, 1993.
15. Sabatier L, Dutrillaux B, Martin MB. Chromosomal instability. Nature 357:548, 1992.
16. Sabatier L, Lebeau J, Dutrillaux B. Chromosomal instability and alterations of telomeric repeats in irradiatedhuman fibroblasts. Int J Radiat Biol 66:611-3, 1994.
17. Roy K, Kodama S, Suzuki K, Watanabe M. Delayed cell death, giant cell formation and chromosome instability induced by X-irradiation in human embryo cells. J Radiat Res 40:311-22, 1999.
18. Ojima M, Hamano H, Suzuki M, Suzuki K, Kodama S, Watanabe M. Delayed induction of telomere instability
in normal human fibroblast cells by ionizing radiation. J Radiat Res 45:105-10, 2004.
19. Dugan LC, Bedford JS. Are chromosomal instabilities induced by exposure of cultured normal human cells to
low- or high-LET radiation? Radiat Res 159:301-11, 2003.
20. Holmberg K, Meijer AE, Auer G, Lambert BO. Delayed chromosomal instability in human T-lymphocyte
clones exposed to ionizing radiation. Int J Radiat Biol 68:245-55, 1995.
21. Salomaa S, Holmberg K, Lindholm C, Mustonen R, Tekkel M, Veiderbaum T, Lambert BO. Chromosomal
instability in in vivo radiation exposed subjects. Int J Radiat Biol 74:771-9, 1998.
22. Hofman-Huther H, Peuckert H, Ritter S, Virsik-Kopp P. Chromosomal instability and delayed apoptosis in
long-term T-lymphocyte cultures irradiated with carbon ions and X rays. Radiat Res 166:858-69, 2006.
23. Kadhim MA, Marsden SJ, Wright EG. Radiation-induced chromosomal instability in human fibroblasts: Temporal effects and the influence of radiation quality. Int J Radiat Biol 73:143-8, 1998.
24. Kadhim MA, Lorimore SA, Townsend KM, Goodhead DT, Buckle VJ, Wright EG. Radiation-induced genomic
instability: Delayed cytogenetic aberrations and apoptosis in primary human bone marrow cells. Int J Radiat
Biol 67:287-93, 1995.
25. Tawn EJ, Whitehouse CA, Martin FA. Sequential chromosome aberration analysis following radiotherapy—noevidence for enhanced genomic instability. Mutat Res 465:45-51, 2000.
26. Whitehouse CA, Tawn EJ. No evidence for chromosomal instability in radiation workers with in vivo exposure
to plutonium. Radiat Res 156:467-75, 2001.
27. Tomonaga M. Leukemia study in A-bomb survivors—Past, present and future. Nagasaki Igakkai Zasshi[Nagasaki Medical Journal] 83(Special issue):161-76, 2008 (in Japanese).

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RERF Update Volume 20, Issue 2, 2009

21

Human Interest Notes

Participating in the Health Examination/Consultation
Project for A-bomb Survivors Living in South Korea
Masazumi Akahoshi, Chief
Department of Clinical Studies, Nagasaki[Summary]
A health examination/consultation project for Abomb survivors residing in North and South America
has been conducted for some time under theleadership of the Hiroshima prefectural government,
but no comparable project targeted A-bomb survivors
living in South Korea. A contract for an assistanceprogram for A-bomb survivors residing in South
Korea was signed in August 2003 between the
Nagasaki prefectural government, entrusted by theJapanese government, and the Republic of Korea
National Red Cross, entrusted by the South Korean
government. The aim of the program was to promoteissuance of A-bomb survivor health handbooks for
those residing in South Korea and to help thesurvivors visit Japan to undergo medical treatment.
As part of the program, the health examination/
consultation project was begun in fiscal year (FY)2004. The project’s objectives include “working on
early detection and treatment of disease via healthexaminations, addressing concerns about aftereffectsof A-bomb radiation exposure in cooperation withJapanese A-bomb disease experts, and endeavoring
to enhance the health of A-bomb survivors.”
For the purpose of detecting potential problems
ahead of the FY2005 introduction of the full-scale
project targeting about 2,400 A-bomb survivors

living in South Korea, a pilot consultation project
was performed twice in 2004, once in the rural areaof Hapcheon and once in the cities of Dejong and
Pyeongtaek. On the basis of the results of the trial
runs, it was decided with regard to the proceduresfor the full-scale health examination/consultation
project that health examinations would be performedin advance at regional Red Cross hospitals and thatJapanese physicians would make final diagnoses andprovide health consultation with use of the relevant
laboratory data and clinical findings, in addition to
information from the questionnaire survey conductedon the day of the consultation project.
Ultimately, the first full-fledged round of the
project was conducted in Seoul in June 2005 incooperation with the Seoul Red Cross Hospital. Since
A-bomb survivors reside throughout the country, theproject was subsequently performed biannually in
Tegu, Hapcheon, Busan, Masan, Gwangju,
Pyeongtaek, and Dejong, where a relatively large
number of survivors live, with support from therespective regional Red Cross hospitals, for a totalof nine times through September 2009. The second
cycle of the project is currently under way. Everyround of the relevant project garners particularly highinterest among A-bomb survivors residing in South
Korea: about 72% of the target population has
undergone health examinations atregional Red Cross hospitals, and about
83% of that number have participated in
the final diagnoses and health consultation conducted by Japanese physicians.

Members of the health examination/consultation team for A-bomb
survivors living in South Korea including Korean collaborators.
Dr. Masazumi Akahoshi is the fourth person from the right in thefront row.

Return to Table of Contents[Details of the health examination/
consultation project for A-bomb
survivors]
The health examinations conducted inadvance at regional Red Cross hospitals
are classified into two types: comprehensive health examinations (exclusively for
those with A-bomb survivor health handbook and/or certificate acknowledging
A-bomb exposure) and basic healthexaminations (for those without therelevant handbook/certificate). The
contents of the comprehensive examination are considered equal to those of theregular health examinations conducted
RERF Update Volume 20, Issue 2, 2009

Human Interest Notes
under the Adult Health Study (AHS). Based on the
results of laboratory tests, physicians at the regional
Red Cross hospitals indicate a preliminary, comprehensive diagnosis and describe overall findings(in notes to participants) in medical charts, which
are translated into Japanese by the translation staff
from the Republic of Korea National Red Cross. With
regard to the tests—electrocardiogram, chest X ray,computerized tomography, gastric endoscopy,
abdominal ultrasonography, and mammography—
actual images are borrowed from the respective
hospitals and are used as needed during final
diagnoses/health consultations. In this regard, I havethe utmost respect for the efforts made by the staff
in charge of such operations. In collaboration with
the Takashi Nagai Memorial International Hibakusha
Medical Center, Nagasaki University Hospital, andthe Republic of Korea National Red Cross, a databasefor laboratory data and names of diagnosed diseases
obtained under the health examination/consultation
project was established one year ago. We are allowed
access to this useful database and permitted to utilize
the data in making our final diagnoses and conducting
the health-consultation activities. As if this work
provided a good opportunity to forge international
relationships, a Japanese physician from the medical
center apparently married a Korean staff member
from the Red Cross sometime this year.
On the day of the final diagnosis/health consultation, volunteer nurses performed body temperatureand blood pressure measurements, as well as
conducted a questionnaire survey. On the basis of
the health examination results, which were translated
into Japanese, and information from the relevant
questionnaire survey, we Japanese physicians took
about one hour to talk to each of the participants,
explain about the relevant health issues, and makefinal diagnoses. We also gave advice to Korean
physicians regarding detailed examinations and/or
provided guidance on courses of treatment. Different
from the health examination program targeting Abomb survivors in North and South America, veryfew Korean participants were able to understandJapanese, and even though some participants could
pick up on the meaning of Japanese conversation,
they were unable to speak. Consequently, interpreters, whose dedication has always impressed me,
were assigned to each physician for support.
I had the impression that a large number of Korean

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22
people suffer from back/knee pain, presumably due
to the South Korean lifestyle on the ondol, or heated
Korean floors. This was the reason for including in
the project team an orthopedic surgeon, a physicaltherapist, and a nurse that instructed the participantsin calisthenics. In South Korea, rehabilitation
following orthopedic surgery is lacking, and hence
guidance for rehabilitation by the physical therapist
and calisthenics instruction by the nurse wereapparently well received among those concerned.
Observed among many A-bomb survivors living
in South Korea are such lifestyle diseases as obesity,
fatty liver, hypertension, diabetes, and cancer,
not very different from the diseases in Japan. In
Hapcheon, however, in a first for the Japanesephysicians, several participants suffered fromclonorchiasis, presumably due to their custom ofeating raw river fish.
Many of South Korea’s A-bomb survivors alreadyhave either A-bomb survivor health handbooks or
A-bomb exposure certificates and thereby receive
medical allowances. For those who do not possess
those two documents, however, staff members fromthe Nagasaki prefectural and municipal governments
and South Korea’s Red Cross provide consultation
services concerning acquisition of such materials.
Furthermore, the staff members provide consultation
services concerning administrative procedures
relating to applications for health management
allowance, A-bomb disease recognition, the assistance project for medical treatment in Japan, andother issues.
With regard to the full-scale project, each team istypically composed of four internal medicine
specialists, one orthopedic surgeon, one physicaltherapist, one nurse, and four employees of theNagasaki prefectural and municipal governmentsfrom Japan; and one physician, nine employees fromSouth Korea’s Red Cross, eight interpreters, six
volunteer staff members from the Red Cross, andfour volunteer nurses from South Korea. With regard
to successful completion of the total of nine roundsof the health examination/consultation project for Abomb survivors residing in South Korea carried out
thus far, I would like to express my great appreciation
for the cooperation and mutual understanding of
those concerned, with the hope that any future
projects yield fruitful results.

RERF Update Volume 20, Issue 2, 2009

23

Human Interest Notes

Work at the Nursing Sections in
Hiroshima and Nagasaki
When ABCC started its research in 1947, there
were only two nurses. As the research project
developed, however, additional nurses wererecruited, and by the time of initiation of the Adult
Health Study (AHS) 50 years ago, the nurses
numbered 40 and 16 in Hiroshima and Nagasaki,
respectively. The nurses were required to work undercircumstances quite different from those of othermedical organizations, and with by paying special
attention to the study participants’ feelings, they
contributed significantly to the development of
nursing at ABCC-RERF and to the success of theinstitution. The observations below are excerpted
from the writings of current chief nurses MichikoKuwamoto (Hiroshima) and Yumiko Yamashita(Nagasaki) reflecting back on the 50th anniversaryof AHS and the 25 cycles of biennial examinations.

students. To persons who know only modern-day
prosperity, this may be a laughing matter, but backthen, for example, we saw paper towels for the firsttime and were shocked to know that these towels
were disposable. We could not help folding andkeeping used paper towels on the edge of a shelf outof thrift—a habit that would evoke Ms. Cavagnaro’s
chiding ‘No good!’ to our embarrassment.”
ABCC received patients and the nurses periodically rotated themselves between the sickroom andthe outpatient department. The sickroom wasequipped with about 10 beds, and the majority ofpatients had blood-related disorders. There weremany U.S. physicians at ABCC then, and thehospitalized study participants may have had anuneasy feeling stemming from communicationdifficulties with these American doctors so it is not
hard to imagine that the nurses at that time had manyIn the early stage of AHS there was a long series
challenges. Of the outpatient department, a formerof struggles and adjustments. The first director ofchief of nurses remembers: “Flow of medical
the ABCC nursing staff was Ms. Louise Cavagnaro
consultation at that time was different from that offrom the U.S. The second director, the late Ms.
today. Examinations and consultation by Japanese
Chiyoko Watanabe from Japan, wrote in her memoir
doctors would be followed by checks by American
about the early days of ABCC: “Post-war Japanese
doctors. During the waiting time in between, somemedicine, nursing in particular, developed with an
study participants would start telling stories involving
American influence. ABCC was a place where suchthe atomic bombings. The stories were often painful
an influence could be felt firsthand. We could learn
for us to listen to; however, we found that such stories
many things through our daily work, as if we were
were very important to enable us to really understandstudying aboard. We were surprised at everything
the survivors’ concerns and feelings, and to fully
we saw or heard just like we were still nursing
comprehend the disastrous events that occurred in
Hiroshima and Nagasaki.”In 1972, there were changes
in the work of the nurses. The
sickroom, where treatment took
place, was closed, and in addition to the clinical examinations,
ABCC staff visited the homes
and hospitals of study participants who were unable to visit
ABCC. Staff were each assigned
to visit 2–3 persons in a half-day
time period. Due to busy schedules, the staff often had justenough time for only examinations and little time for conversation with the participants. In
the limited time, however, staff
tried to talk with the participants
and provide as much advice aspossible. The ABCC staff iniNursing Section staff in 1953, Hiroshima Laboratory
tially wore a white robe to visit
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RERF Update Volume 20, Issue 2, 2009

Human Interest Notes
the participants, but were told that the participants
did not like to receive persons in white, because suchclothes would catch the attention of their curious
neighbors. So the staff began conducting the visits
wearing street clothes and a name tag. They also
reevaluated the gown and slippers, into which theparticipants changed at the clinical department,
and made necessary changes for the participants’convenience and comfort.
It was important for the nurses to understand aparticipant’s individual feelings and circumstances.
For example, some unwillingly visited ABCC for
examination because they could not refuse therepeated requests from ABCC staff, or visited ABCC
unwillingly because the staff came over to pick themup. Paying close attention to the participants’feelings, making their visits as comfortable aspossible, and sending them home without any
problems were all part of the mission of the nurses
and something they always kept in their minds as anattitude that has been maintained since the earliest
ABCC years.
ABCC sometimes received thank-you letters fromthe participants after examinations, and often theseletters said, “You listened to my stories well,” or “Yougave me appropriate advice.” Unlike the visitors toother hospitals, a majority of those visiting ABCCRERF were relatively healthy persons who wereasked to take time to visit Hijiyama, who sometimes
took our well-intentioned health tips as something
uninvited, and who often were required to stay at
RERF for a prolonged time to fill out lengthy
questionnaires. Since our participants who provide
support to the AHS are aging, nurses are required tochange their approaches and always seek better
approaches.
The Nursing Section has made a continued effort
to develop trust with the study participants byproperly treating individual participants, in the hopethat all participants will visit the organization again
for examinations every two years. There have been
participants, who complained about the foundation,
were upset about the content of questions requiring
lengthy answers, or who indignantly questioned thenurses why their diseases had not been detected
earlier despite their continued participation in
examinations for years. Some said that they would
never come for the examinations again. If we hadsuch participants as described above, we madecontact with the Clinical Contacting Section and tried
to accurately tell them why the participants were
unsatisfied or unhappy, so that the contactors could
utilize our report when they contacted the participantsin the future.
In the early years, the survivors were often in poor
hygienic and nutritional conditions, and some visitors

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to ABCC were suffering from infectious diseases.
On such occasion, extra care was paid to prevent
infection at ABCC, and after the examinations, theexamination room including its walls was wiped with
antiseptic solution, and used linen was all disinfected.
Iron was prescribed for participants with anemia until
their conditions returned to normalcy. Also, there
were some participants with persistent generaldermatitis, which was cured by ABCC’s ointmentthat gave the survivors great comfort. Special
examinations in the Nursing Section included agastrocamera and a bone marrow puncture.
Participants suspected of leukemia underwent bonemarrow puncture and were introduced to hospitals
with their examination records from ABCC.
Although the Nagasaki Laboratory did not receive
patients for treatment, medicine was prepared there
also and, according to the doctors’ instructions,limited provision of medicine was available for thosewith the above-mentioned anemia and skin disease.
Ms. Cavagnaro also visited Nagasaki to instruct
the staff there. Based on a translated version ofManual of Nursing Procedures, she prepared nursing
procedures for the staff, which have been modified
for use. In 1967, a revised version was prepared by
Chief Watanabe of the Nursing Section in Hiroshima
and others, and later, a third revision was published.
The late Ms. Teiko Ohki, who served as a chief of
the Nursing Section in the early years of AHS, wrote
about the directions for nurses as follows: “Nurses
are persons who can understand the basic mattersrequired for human health and best respond to thepersons in need of such matters. To achieve theirgoals, nurses must acquire knowledge in nursing inline with scientific progress of the society, fully
utilize the knowledge as required by individuals or
society, and have an ability to collaborate/cooperatewith other specialists including physicians andpharmacists. At ABCC in particular, nurses are also
required to try their best to create an environment,
in which the study participants can feel a sense oftrust and safety.”
Since ABCC was an organization conducting
epidemiological research, standardizing protocol
procedures was most important. That required
maintaining close contact between the Hiroshima andNagasaki Laboratories. The success of the AHS
examinations owes much to the Hiroshima andNagasaki nurses for their consistent performance ofmultiple tasks, their required skills, and for theirpatience and understanding in being the primarycontact with the AHS participants. As Ms. Yamashitasummarized: “To this day, there are many participants
who nostalgically mention the names of some former
nurses, and I feel that a trust has long been establishedbetween the participants and the Foundation.”

RERF Update Volume 20, Issue 2, 2009

25

Human Interest Notes

In Memoriam
The RERF family was saddened to learn that
Victoria Margaret Schull, the wife of William J.
Schull, died on October 13, 2009 after a prolonged
illness. Born March 11, 1922, Mrs. Schull was 87
years old. She and Dr. Jack Schull had recently
celebrated their 63rd wedding anniversary. “Vicki”
as she was affectionately known, joined her husband
in Hiroshima in 1949 during the early days of ABCC,
shortly after Jack was hired by the National ResearchCouncil to join ABCC, and as soon as housing
became available in Hiroshima. Vicki embraced
Japanese culture, became proficient in speaking
Japanese, and her companionship helped serve as aninspiration to Jack for his frequent service to ABCC
and RERF over a period of almost 50 years, including
holding the position of Vice Chairman and Chief ofResearch as late as 22 January 1997.

Return to Table of Contents

William Jack (left) and Victoria (center) Schull withformer RERF chairman Itsuzo Shigematsu (right) ata farewell party in 1987

RERF Update Volume 20, Issue 2, 2009

26

Facts and Figures

RERF Staff’s Strengths Demonstrated
at Open House Events
Takanobu Teramoto, Permanent Director
RERF held Open House events on August 5 and6, 2009, in Hiroshima and on August 8 and 9 inNagasaki, with this year marking the 15th and 13thof the annual summer events, respectively. Somevisitors attend the Open House every year, such as
A-bomb survivors, local citizens, and employee
family members, while some individuals from allover Japan and the world for that matter visit RERF
for the first time on the dates commemorating theatomic bombings of Hiroshima and Nagasaki. Taking
the opportunity presented by the Open House to
publicize RERF’s activities, we start preparations forthe events around the beginning of each year bydeciding on the year’s event theme and specific plans.
Then in the spring of the year we establish OpenHouse working committees. This year’s theme was“Radiation and health sciences founded on the basisof international cooperation,” a future-oriented theme
that reflects RERF’s commitment to expand its
research collaborations and become a global centerof excellence, as stated in its future plans. In thespecial exhibition on this theme, RERF’s worldwide
collaborations with research institutes andinternational agencies, researchers visiting RERF
from various parts of the world for training, andRERF researchers’ global activities were introduced
using a world map. We felt very encouraged whenseveral visiting Japanese Diet members, who wereastounded to know that RERF’s international
collaboration extends to five continents throughout
the world, promised their firm support for RERF.
Of special note about this year’s events is that

employee participation was further strengthened andemployee ingenuity was utilized in numerous ways.
In addition, as part of employee training, some ofour staff members studied how to greet and welcome
visitors and put such instructions into practice at thetime of the Open House. Cooperation and coordination between Hiroshima and Nagasaki Laboratories were also enhanced through preparations anddisplays of posters and leaflets.
Visitors totaled 617 and 566 in Hiroshima andNagasaki, respectively. The turnout in Hiroshima wasdown considerably from last year’s 1,355, due toactivities related to the Lower House elections.
However, there was also a positive side to the lower
numbers, because we were able to spend more timewith each visitor and explain our operations in moredetail. The turnout in Nagasaki was higher by asmuch as 46%, compared with last year’s 388.
Although the Nagasaki event also was held during
the election campaign, the efforts of the Nagasaki
Laboratory staff to publicize the event proved
particularly effective. They allowed day-care
programs for school children during the summer
vacation to incorporate the RERF visit into theireducation programs. On the days of the events,
children took turns looking at their own bodies’ cellswith a microscope and watched flowers being frozen
solid by –196°C liquid nitrogen. It probably was theirfirst science experiment.
The Open House in Nagasaki this year was held
on Saturday and Sunday. For that reason, the event
must have been a burden on the staff and their

After a swab of their mouths, children were able to look through a microscope at their own buccal cells at OpenHouse 2009, Nagasaki Laboratory

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RERF Update Volume 20, Issue 2, 2009

27

Facts and Figures

Number of Visitors to RERF Open House
Year

2004

2005

2006

2007

2008

2009

Hiroshima

850

1,062

1,382

967

1,355

617

Nagasaki

230

306

528

484

388

566

Total

1,080

1,368

1,910

1,451

1,743

1,183

families. The staff in Hiroshima had the same
experience a few years ago. However, considering
the meaning of the A-bombings for the mission andresearch activities of RERF, we have maintained thepolicy of holding the Open House events on theanniversary of the atomic bombings, and the previous
day in each city.
Meanwhile, the Green Club at Hiroshima RERF

grew beautiful sunflowers in time for the OpenHouse. The typical impression of a research
institute—indifferent and unfriendly— seems to havevanished from RERF over the years. I would like toexpress my sincere appreciation to all directors andstaff at RERF and the RERF Labor Union for theircooperation and support during the Open House
events.

DS02 Errata
It is not unexpected that in the course of publishinga two-volume treatise such as the revised dosimetry
for the A-bombs (DS02), that subsequent review
would yield some typographical or technical errors.
The following errata have been called to RERF’s
attention:
Chapter 4, Table 5A, page 240: In the title of thetable, change the first coordinate of the DS02
hypocenter from “27.721” to “26.721.”

Group
NumberNeutrons
3
4
19
20
21
22
43

Upper energy
bound (MeV)(previously published value) correct value(1.45E+1)(1.40E+1)(2.05E+0)(1.61E+0)(1.26E+0)(1.03E+0)(5.71E-5)

1.49E+1
1.42E+1
2.31E+0
1.83E+0
1.42E+0
1.11E+0
1.07E-5

Chapter 12, Table 7, page 844: In the section of
the table for Neutrons, replace the energy group upperbounds as follows:

Return to Table of Contents

RERF Update Volume 20, Issue 2, 2009

Research Protocols

Research Protocols Approved in
April–September 2009
RP 1-09 A Nested Case-Control Study of Factors Contributing to Acceleration of the Development of Hepatocellular Carcinoma Using
Stored Sera (Addendum to RP 1-04)
Ohishi W, Fujiwara S, Cologne JB, Akahoshi M,
Nishi N, Suzuki G, Tsuge M, Chayama K
This research protocol is an addendum to RP 104. The objective of RP 1-04 is to study the effectsof radiation exposure, hepatitis virus infection, andlifestyle-related factors on the risk for developmentof hepatocellular carcinoma (HCC). In this study,
we indicated that hepatitis B virus and hepatitis C
virus infection, obesity, and alcohol consumption are
independent risk factors for HCC. Furthermore, theongoing analyses suggest that radiation exposure
may contribute to increased HCC risk, irrespectiveof hepatitis virus infection. With this addendum
protocol, we will measure biomarkers related tochronic inflammation and/or insulin resistance thatare considered important factors contributing toacceleration of the development of HCC using storedsera among subjects of this nested case-control study(RP 1-04), as well as examine their contribution to
HCC risk.
RP 2-09 Study on Secondary Cancer Risks
after Radiotherapy among A-bomb Survivors
Yoshinaga S, Nishi N, Soda M, Akahane K, Doi K,
Moriwaki H, Hsu WL, Hida A, Yamada M, Katayama
H, Shimada Y, Fujiwara S, Akahoshi M, Suyama A,
Kasagi F, Ozasa K
The studies of cancer risks among A-bomb
survivors have mainly focused on the relationshipwith A-bomb radiation, and less attention has been
paid to other sources of radiation. The primary goalof this study is to evaluate the combined effects of
the A-bomb radiation and therapeutic radiationdelivered at two different times. The study population
is a subgroup of members of the Life Span Study
who were confirmed to undergo radiotherapy in thepreceding study. Outcomes of primary interest arecancer incidence and mortality after radiotherapy. In
addition to analyzing risk of second cancers in
relation to therapeutic radiation dose, we will also
analyze the modification effects of A-bomb radiationon the second cancer risk associated withradiotherapy. This study will provide new insight into
the possible effects of two different types of radiationdelivered at different times on cancer risk.
RP 3-09 Development of an Integrated Scoring
System for Human Immune Competence as It
Relates to Age and Ionizing Radiation
Hayashi T, Kusunoki Y, Imai K, Yoshida K, Ito R,
Return to Table of Contents

28
Ohishi W, Fujiwara S, Ozasa K, Furukawa K, Geyer
SM, Weng NP, Sempowski GD, Yasutomo K,
Koyasu S, Murasko D, van den Brink MRM, Manley
NR, Nikolich-Zugich J, Hirabayashi Y, Iwama A,
Inoue T, Inaba K, Seed TM, Douple EB, Nakachi K
RERF’s epidemiology and clinical studies havelong indicated that there are significant increased
risks of age-related and immune system/inflammation-related diseases among A-bomb survivors.
Further, the noted radiation effects on the immune
system are similar to those associated with simple
aging. The objective of this study is to develop an
integrated scoring system for evaluating immunological and inflammatory status of individuals as
a function of age and radiation dose, and predicting
the effects of radiation on the immune system andsomatic mutation in exposed subjects. A crosssectional analysis is proposed that will include about
2,300 Hiroshima Adult Health Study (AHS) subjects
as well as an additional 1,300 subjects in an extended
AHS cohort of Hiroshima survivors. A longitudinal
analysis is proposed that will include a subset of 300
AHS subjects randomly selected from the 2,300 AHS
subjects who had samples collected between 2000–
2002 and will use stratified random sampling basedon radiation dose group, age group, and gender.
Biomarkers will be measured on 600 plasma samples
collected from the 300 AHS subjects using antibody
chip arrays. Two samples will be used for each of
the randomly selected subjects; those collected
between 2000–2002 and those collected between
2010–2012, resulting in sets of samples about 10
years apart. Telomere length assays will also be
conducted on DNA from the same 600 samples.
Effects of radiation exposure on aging markers in
the thymus will be evaluated based on pathologicalreview and molecular analysis. The results will beutilized to construct integrated scoring systems that
effectively reflect overall immune-related health, andhow that immune status differs across varying age
and radiation groups.

RP 4-09 Effects of Ionizing Radiation Exposureand Aging on Vaccination Responses
Hayashi T, Kusunoki Y, Imai K, Yoshida K, Misumi
M, Ohishi W, Fujiwara S, Ozasa K, Geyer SM,
Yasutomo K, Koyasu S, Sempowski GD, MuraskoD, van den Brink MRM, Weng NP, Manley NR,
Nikolich-Zugich J, Hirabayashi Y, Iwama A, Inoue
T, Inaba K, Seed TM, Douple EB, Nakachi K
Our past studies have revealed that radiation
exposure was associated with reductions in therelative numbers of naïve T cells and IL-2-producing
cells, both of which are closely involved indetermining an individual’s protection in response
to vaccination. In addition to an impaired immune
system, the tendency of a persistent inflammatory
response is still observed in some of the atomic-bomb
RERF Update Volume 20, Issue 2, 2009

Research Protocols(A-bomb) survivors, even more than 60 years after
the A-bombings. Therefore, it is important toexamine whether the impaired immune system
results in a modified vaccine response among Abomb survivors. This study is designed to evaluate
the effects of prior A-bomb radiation exposure on
the immunological capacity of aging individuals to
respond to influenza vaccination. We will recruit 50
subjects for a pilot study and 300 subjects for the
full-scale study by stratified random sampling of dosegroup, age group, and gender. Adult Health Study
subjects will be recruited to this study over a periodof three years. Collection and storage of blood plasma
and lymphocyte samples will be conducted before
and three weeks after the vaccination. The primary
endpoint will be the change in anti-influenza virus
antibody titer levels from before to three weeks after
vaccination. Secondary endpoints to be analyzed
include levels of cytokines and inflammation-related
proteins, lymphocyte subsets, intracellular activation
markers (mRNA and protein), and HLA genotype.
Those parameters will be analyzed in relation to age
and dose of prior radiation exposure.

29
self-renewal and differentiation potentials of HSCs
will also be analyzed at another laboratory in the
United States (Memorial Sloan-Kettering Cancer
Center) if methods for these HSC functional assays
cannot fully be introduced at RERF. Finding
significant alterations in the numbers and functionsof circulating HSCs in relation to age and radiationdose would support our working hypothesis that
A-bomb irradiation accelerated aging of thelymphohematopoietic system. Further, if significant
alterations in the numbers and functions ofcirculating DCs are observed as well (i.e., in relation
to age and radiation dose), this would support our
hypothesis that A-bomb irradiation affected primary
and adaptive immunity, possibly by altering DC
populations toward T-cell inhibitory types. In orderto support these A-bomb survivor studies, we willdevelop a series of in vitro and in vivo assay systems
for the purpose of a) determining the functional anddifferentiation status of HSC and DC populations
following in vitro or in vivo irradiation, and b)
uncovering radiobiological mechanisms of
immunosenescence relative to HSC and DC populations.

RP 5-09 Effects of Radiation Exposure andAging on Hematopoietic Stem Cells (HSCs) and
Dendritic Cells (DCs)—Analyses of Numericaland Functional Changes
Kusunoki Y, Yoshida K, Hayashi T, Geyer SM,
Misumi M, Ohishi W, Fujiwara S, Ozasa K,
Hirabayashi Y, Iwama A, Koyasu S, Yasutomo K,
Inoue T, Inaba K, Manley NR, van den Brink MRM,
Sempowski GD, Nikolich-Zugich J, Weng NP,
Murasko D, Seed TM, Douple EB, Nakachi K
Sufficient ionizing irradiation can diminish
homeostatic control of blood cell production,
including the primary cells comprising the immune
system. Recent mouse studies suggest that advancing
age is associated with a deficiency in the maintenanceof hematopoietic function as well as an effect on
adaptive immunity. Dendritic cells (DCs) are thought
to be crucial, not only in triggering primary immune
responses against pathogens, but also in the controlof adaptive immunity. To delineate the long-term
consequences of prior A-bomb irradiation andadvancing age on homeostatic control of hematopoietic
stem cells (HSCs) and DCs, we will analyze
numerical and functional changes within thecirculating HSC and DC pools among several
hundred individuals who are currently participatingin the Adult Health Study (AHS) at RERF in
Hiroshima. Although blood samples to be provided
by the AHS participants will primarily be analyzed
at RERF, some of the assays will be done outside
RERF by collaborating investigators, i.e., DC
functional molecules will be assessed at a laboratory
in the United States (Duke University) using total
RNA/culture supernatant from DC cell fractions; andReturn to Table of Contents

RERF Update Volume 20, Issue 2, 2009

30

Recent Publications

Recent Publications(Japanese): the original article is in Japanese.

Fujiwara S. Lifestyle and bone mineral density.
Seijinbyo to Seikatsu Shukan-Byo [The Journalof Adult Diseases] 2009 (May); 39(5):519-23.
(Japanese)
Fujiwara S. Osteoporosis and compression fracture—
Epidemiology of osteoporosis. Rinsho Gazo
[Clinical Imagiology] 2009 (August); 25(8):8227. (Japanese)
Fujiwara S. Fracture risk assessment using a FRAX®.
Ryumachi-ka [Rheumatology] 2009 (March);
41(3):299-305. (Japanese)
Furukawa K, Cologne JB, Shimizu Y, Ross NP. Predicting future excess events in risk assessment.
Risk analysis 2009 (June); 29(6):885-99. (RERF
Report 6-08)
Grant EJ, Shimizu Y, Kasagi F, Cullings HM, Shore
RE. Radiation unlikely to be responsible for highcancer rates among distal Hiroshima A-bomb survivors. Environmental Health and Preventive
Medicine 2009 (July); 14(4):247-9. (RERF Commentary and Review Series 1-09)
Hamasaki K, Kusunoki Y, Nakashima E, Takahashi
N, Nakachi K, Nakamura N, Kodama Y. Clonallyexpanded T lymphocytes from atomic bomb survivors in vitro show no evidence of cytogenetic
instability. Radiation Research 2009 (August);
172(2):234-43. (RERF Report 16-08)
Ohishi W, Tsuge M, Chayama K. Hepatitis B virus
genotypes and prognosis of chronic hepatitis B.
Rinsho Shokaki Naika [Clinical Gastroenterology]
2009 (June); 24(6):653-9. (Japanese)
Okubo T, ed. Ministry of Health, Labour and Welfare
Grants: FY2008 Report of Atomic Bomb Disease
Research Project. 2009 (July), 81 p. (Japanese)
Richardson DB, Sugiyama H, Nishi N, Sakata R,
Shimizu Y, Grant EJ, Soda M, Hsu WL, Suyama
A, Kodama K, Kasagi F. Ionizing radiation andleukemia mortality among Japanese atomic bomb
survivors, 1950–2000. Radiation Research 2009
(September); 172(3):368-82. (RERF Report 2-09)
Richardson DB, Sugiyama H, Wing S, Sakata R,
Grant EJ, Shimizu Y, Nishi N, Geyer S, Soda M,
Suyama A, Kasagi F, Kodama K. Positive associations between ionizing radiation and lymphoma
mortality among men. American Journal of Epidemiology 2009 (April); 169(8):969-76. (RERF
Report 8-08)

Return to Table of Contents

Shore RE. Low-dose radiation epidemiology studies: Status and issues. Health Physics 2009;
97:481-6.
Takahashi N, Satoh Y. Studies of trans-generational
effects following A-bomb irradiation. Tanaka S,
Fujikawa K, Ogura K, Tanaka K, Oghiso Y, eds.
Carcinogenesis and Genetic Effects of Low Dose
Radiation Exposure. Aomori: Institute for Environmental Sciences (IES); Proceedings of theInternational Symposium on Carcinogenesis andGenetic Effects of Low Dose Radiation Exposure
2008 (October), pp 15-9.
Takahashi N, Satoh Y, Kodaira M, Katayama H.
Large-scale copy number variants (CNVs) detected in different ethnic human populations.
Kehrer-Sawatzki H, Cooper DN, eds. Copy Number Variation and Disease. Basel: Karger; 2009,
pp 224-33.
Toyoshima M, Young XI, Kubo K, Hamasaki K,
Kusunoki Y, Honda H, Masuda Y, Watanabe H,
Kamiya K. Role of Rev1 in N-methyl-Nnitrosourea induced mutagenesis and tumorigenesis. Nagasaki Igakkai Zasshi [Nagasaki Medical
Journal] 2008 (September 25); 83(Special issue):367-9. (Proceedings of the 49th Late A-bomb
Effects Research Meeting, 2008) (Japanese)
Yamada M, Mimori Y, Kasagi F, Miyachi T, Ohshita
T, Sasaki H. Incidence and risks of dementia inJapanese women: Radiation Effects Research
Foundation Adult Health Study. Journal of the
Neurological Sciences 2009; 283:57-61.
Yoshida K, Kubo Y, Kusunoki Y, Morishita Y,
Nagamura H, Hayashi I, Kyoizumi S, Seyama T,
Nakachi K, Hayashi T. Caspase-independent cell
death without generation of reactive oxygen species in irradiated MOLT-4 human leukemia cells.
Cellular Immunology 2009 (March); 255:61-8.
(RERF Report 10-08)

Publications Using RERF Data
The following publications represent research done
by non-RERF scientists based on the data publicly
available from RERF.
Little MP. Cancer and non-cancer effects in Japanese atomic bomb survivors. Journal of Radiological Protection 2009 (June); 29(2A):A43-59.
Little MP. Heterogeneity of variation of relativerisk by age at exposure in the Japanese atomic
bomb survivors. Radiation and Environmental
Biophysics 2009 (August); 48(3):253-62.

RERF Update Volume 20, Issue 2, 2009