Table of Contents
From the Editors ......................................................................................................................................... 1
RERF NewsThe 50th Anniversary of Commencement of the Adult Health Study, by Toshiteru Okubo ................ 1
The 36th Scientific Council Meeting .................................................................................................... 3
Staff News ............................................................................................................................................. 5
Honors and Awards Received by RERF Scientists ............................................................................... 6
Conference and Workshop Reports
Workshop on Radiation Risk of Breast Cancer, by Nori Nakamura ..................................................... 7
Radiation Cataractogenesis Workshop, by Kazuo Neriishi .................................................................. 8
Science Article
What and How Large Are the Risks from Prenatal (In Utero) Radiation Exposure?
by Roy Shore, Misa Imaizumi, Yoshimi Tatsukawa, and Nori Nakamura ....................................... 9
Human Interest Notes
Taking Early Retirement, by Yukiko Shimizu .................................................................................... 13
Recontacting Work, by Toshiko Tsukamoto ....................................................................................... 14
In Memoriam ...................................................................................................................................... 16
Facts and Figures
RERF Research: Themes, Prioritization, 5-year Program Goals, Interdepartmental Programs,
and a New Contract with the U.S. National Cancer Institute, by Roy Shore ..................................... 17
Research Protocols and Publications
Research Protocol approved in October 2008–March 2009 ............................................................... 18
Recent Publications ............................................................................................................................. 18

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
Subarashii!
That word was heard a lot around RERF again as
Hijiyama’s sakura season finally arrived and blossoms were in full bloom. It was difficult schedulingohanami parties this year since the cool weather
delayed the opening of the buds over a long periodof time—as if nature was stretching out this magnificent season. We guess that Seymour Abrahamson
would have called some of them “o-ha-mi” (or “leafparties”). But when the warm weather finally arrived,
the final burst of beauty was a sight to behold—kirei!
While there are many sakura trees visible from within
RERF, it is actually hard to obtain a photo of thetrees that includes the RERF laboratories. To solvethat problem, we called upon the traffic mirror andput it to another good use.
We are pleased that you have joined us for anotheredition of Update. We want to continue last year’s
revival of biannual issues of Update. In this summer
issue you will find a tribute to the 50th anniversaryof the establishment of the Adult Health Study(AHS), a summary of the 36th Scientific Council
meeting, a review of the studies on A-bomb survivors

who were exposed in utero, and the announcementof the start of a new contract with the U.S. National
Cancer Institute to continue our long-standing
collaborative epidemiological studies of cancer
among A-bomb survivors. As always, we hope thatyou enjoy this issue and don’t hesitate to drop us aline and let us know how we might improve ourreporting of RERF’s many activities.
Ja, mata!

Evan B. Douple
Editor-in-Chief

Yuko Ikawa
Technical Editor

On the Occasion of the 50th Anniversary of Commencement of
the Adult Health Study
Toshiteru Okubo, Chairman
Fifty years have passed since the Adult HealthStudy (AHS), a large-scale epidemiological study ofA-bomb survivors, started in 1958. It is easy to say“50 years,” but this period of time is extremely longfor the loyal survivors who have participated, for the
many scientists who have conducted the study, andfor a binational research institution. The A-bomb
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radiation-exposed members of the general public in
Hiroshima and Nagasaki include persons representing
a wide range of ages, from the very young to theelderly. The survivor who was the youngest at thetime of the A-bombings has now attained the age of
63. Furthermore, the youngest staff member of theresearch organization who was at the age of 20 in
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RERF News
1958 has attained the age of 70—well over the fixed
age of retirement.
The AHS’s characteristics, other than the lengthy
study period and exposures to people of all ages andover a wide range of radiation doses, include a verylarge size of the initial cohort of about 20,000 people.
The A-bombings were unprecedented events inhuman history and, although acute symptoms were
known to a certain extent around that time, no one
knew what the persistent and long-term health effectsof radiation would be. Hence, it was necessary to
conduct the AHS. Generally speaking, the better thequality of the data, the longer the study period orobservation period, and the larger the cohort size inan epidemiological study, the more likely the chanceof elucidating statistically significant effects andassociations which are relatively small or rare withimproved sensitivity and accuracy. Therefore, the
AHS’ long followup, large cohort size, and faithfulcontributions of its many survivor participants havebeen indispensable for the identification and studyof the health effects of A-bomb radiation.
The AHS was started during the days of theAtomic Bomb Casualty Commission (ABCC), which
was established by the U.S. government and which
was the predecessor of the Radiation Effects
Research Foundation (RERF). The government that
had dropped the A-bombs introduced this study andthat fact influenced the feelings of AHS participantsaround that time. I understand that some people had
doubts about the objectives of the study and decided
not to cooperate, and that is understandable. Today,
however, 50 years later, no one has doubts about thesignificance of the medical findings related to thelong-term effects. Thus, AHS has been contributing
greatly to science and to the welfare of human beings.
It is impossible to calculate the number of all of
the people who have contributed to or supported thisimportant study in a direct and/or indirect manner. It
is assumed that the number of RERF staff members
who engaged in this study exceeds 1,000 or even
2,000. In light of the factors mentioned previously,
it is certain that AHS is an historic and impressively
large-scale accomplishment of considerable
importance in the field of medical sciences.
The achievements of the AHS as a medical study
have been disseminated world-wide through a large
number of papers published in scientific journals.
However, it is said that with regard to epidemiological research, the results of the research which can bequantified, generalized, and expressed as conclusions
in a scientific paper usually account for less than 10%of the total information collected which is available
for future research and discoveries. And there isalso a humanitarian aspect to the AHS. For example,

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when one takes
into account thedifficult situation
under which the Abomb survivors
were placed during the early years
often called a “decade-long hiatus,”
medical staff who
were engaged in
AHS worked very
Toshiteru Okubo, Chairman
diligently and musthave met a large
number of A-bomb survivors in the course of starting and conducting the study during difficult times,
and they shared the A-bomb survivors’ joys andsorrows. Furthermore, the staff members must haveseen changes in lifestyles, aging of the A-bomb
survivors, and the passage of time as the two cities
were reconstructed from the ashes of the A-bombings. This required patience, dedicated hard work,and understanding.
In epidemiological research, the importance ofsuch social and medical observational findings thatare brought about through relationships of theresearchers among people in the course of interviews
and/or health consultations cannot be adequately
described in scientific papers and should not beignored. This is different from experiments involving cultured cells or from animal experiments in thatepidemiological data are often generated throughinterpersonal relationships. The strength of thoserelationships which accompanies the acquisition ofdata is said to be a secondary gain for the researchers and often contributes to the success of the study
and the reliability and quality of the scientificresearch. Thus, rich and historical observational data
exist behind statistically quantified, scientificachievements, and the resource remaining for futurescientists of the AHS is no exception. And unless all
information is taken into account in epidemiological research, false conclusions can be drawn.
Since many ABCC and RERF staff members who
were involved with the AHS have left RERF, thenumber of people who can testify about the past days
is limited. We would like to introduce a memoir (asone of the “Human Interest Notes” on page 14 ofthis issue of Update) of a former ABCC employee
who served for many years as a contactor and whotalked directly to A-bomb survivors to ask for theircooperation and who was intimately involved in
obtaining and preserving the valuable records of thehumanitarian or so-called “secondary researchachievements.”

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RERF News

Report on the 36th Scientific Council Meeting
The 36th Scientific Council (SC) meeting to review research progress and plans at RERF was heldon March 2–4, 2009 at RERF in Hiroshima. It wasco-chaired by Drs. Katsushi Tokunaga and David
Hoel. Two new members joined the SC, Dr. Sally
Amundson (Columbia University) and Dr. Kiyoshi
Miyagawa (The University of Tokyo). The pattern
begun the previous year of augmenting the intensive review of selected departments by adding several
ad hoc Special SC members was again followed, withthe addition of Drs. Ranajit Chakraborty, Yoshiya
Shimada, and Gen Suzuki to enhance the review of
the Genetics and Radiobiology/Molecular Epidemiology Departments.
Dr. Toshiteru Okubo, Chairman of RERF, expressed
his appreciation for the SC members’ willingness tocome and provide a review of our research program,and emphasized how important SC’s work is to thescientific staff of RERF. He reported that the Senior
Review Panel had issued its final report which
expressed strong support for the continuance of
RERF for the mission of assessing the health risks
to atomic-bomb survivors. He emphasized the need
to follow up the key cohorts, the Life Span Study,
Adult Health Study, in utero, and F1 generation
cohorts, for at least the next 20 years, and to use thedata obtained through them to the best scientificadvantage.
Dr. Roy E. Shore, Vice Chairman and Chief ofResearch, expressed gratitude for the previous year’s
SC review, which has been very helpful to RERF. In
responding to last year’s recommendation that we
better articulate the long-term goals and research
directions of RERF, he indicated that we have now
defined six major research themes and developed afive-year plan oriented toward those themes. Briefly
stated, the research themes are: cancer, cardiovascular disease, other radiation-related health outcomes, genetic effects, immunologic effects, anddosimetry. In response to other recommendations,
he mentioned that we have worked with the respective departments to develop and refine research
priorities; that we now have several examples ofprogrammatic, interdisciplinary research and willcontinue to move further in that direction; that wehave been strengthening our relationships with local
and regional research universities; that we are giving increasing attention to study design and analysis
issues to assure appropriate research methodology;
and that we have devoted considerable attention tointernational collaborative research and to international education and training.
Next, detailed presentations were made by members of the Department of Radiobiology/Molecular
Epidemiology and the Department of Genetics ofReturn to Table of Contents

their research activities and plans, followed by brief
overviews of the activities of the Departments ofClinical Studies, Epidemiology, and Statistics, aswell as the Public Relations program. Subgroups of
SC members then spent several hours in informal
meetings with the various department research staffs.
The SC’s written review began by again notingthat “RERF is the pre-eminent leader in radiation
risk research in the world and has the expertise, populations, and data sets to conduct investigations thatcannot be carried out elsewhere. The support andassistance of the Japanese Ministry of Health, Labourand Welfare and the United States Department ofEnergy, as well as scientific guidance of the National
Academy of Sciences, continue to be crucial to themission of RERF. Without such support and theassistance of the survivors and their families, theability of RERF to conduct superb and substantial
research that has great impact around the world
would not be possible. The mission of RERF has
recently become all the more critical with theincreased international concerns over radiation healthrisks due to: a) the nuclear power option, b) the
increased use of radiation in medical screening andtreatment, and c) the threat of nuclear terrorism.”
They also emphasized that “the world radiation
protection bodies have relied heavily on the risk
values produced by RERF” and noted several recent
examples of this.
A brief summary of their general recommendations is:• The SC commended RERF for the increased
collaboration among researchers through theestablishment of interdepartmental working
groups organized around research themes. They
recommended developing further working
groups, defining comparative study priorities,
and implementing study milestones andtimelines. Integration and efficiency could befacilitated by developing a structure of corefacilities. They also suggested that morethought be given to additional integration of
departments.
• The SC recommended that a working group be
established to develop plans to better integrate
both data and biospecimen management.
• The SC noted that changes in the nature ofscience indicate the need to give high priority
to the development and incorporation of
bioinformatics expertise at RERF.
• The SC recommended increased communication with the A-bomb survivors and community about the collaborative sharing of data andbiospecimens. They suggested that the Public
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RERF News
Relations unit conduct an “augmented programof interacting with cohort members and relatives of victims” and engage “global broadcast
and print media in the mission and story of
RERF.”• The SC noted the importance of increasing therate of first-author publications by the researchstaff.
To highlight a few of the notes and recommendations for departments:• Chromosome aberration analyses applied to inutero exposure are shedding light on the stability of mutations and the dynamics of stem cells,with mechanistic implications regarding theage-dependency of radiation carcinogenesis.
• The study on the immature oocytes of female
rats is important, since it may provide a scientific foundation for male versus female differences in spontaneous and induced rates ofmutations. Moreover, the general public is very
sensitive to radiation risks regarding female
reproduction.
• The SC recommended that radiation-related
genomic deletions be studied in F 1 animalmodels with comparative genomic hybridization using high-density arrays, after which similar studies could be considered in the offspringof A-bomb survivors.
• It is recommended that the F1 clinical study
examine not only common multi-factorialdiseases, but also the frequency and associatedfamily histories of rare dominant Mendeliandiseases, since a de novo occurrence might
indicate a radiation-associated germ cell mutation.
• Immunological senescence as a mechanism forradiation-related cancer and non-cancer diseases is an attractive hypothesis. It is recommended that the Department of Radiobiology/

Molecular Epidemiology more fully examine
newly defined T-cell subsets that may play regulatory roles in autoimmune or inflammatory
diseases, that they also consider innate immunity, and that, in collaboration with the Clinical Studies Department, they examine clinicalcases of immune disease regarding this hypothesis.
• The SC was pleased that a new Chief of Epidemiology, Dr. Kotaro Ozasa, has been recruited,and believes that his leadership will provide an
excellent opportunity for the department toadvance.
RERF Scientific Councilors
Dr. David G. Hoel, Co-chairperson, Distinguished
University Professor, Department of Biostatistics, Bioinformatics and Epidemiology, Medical
University of South Carolina
Dr. Katsushi Tokunaga, Co-chairperson, Professor,
Department of Human Genetics, Division ofInternational Health, Graduate School of Medicine, The University of Tokyo
Dr. Ohtsura Niwa, Deputy Director, Research Center for Charged Particle Therapy, National
Institute of Radiological Sciences
Dr. Yoshiharu Yonekura, President, National
Institute of Radiological Sciences
Dr. Takashi Yanagawa, Professor, The Biostatistics
Center, Kurume University
Dr. Kiyoshi Miyagawa, Professor, Laboratory of
Molecular Radiology, Center for Disease
Biology and Medicine, Graduate School of Medicine, The University of Tokyo
Dr. Marianne Berwick, Professor and Chief, Division of Epidemiology, Associate Director,
Cancer Research and Treatment Center, University of New Mexico
Dr. John J. Mulvihill, Professor of Pediatrics, Uni-

Participants of the 36th Scientific Council meeting held at the Hiroshima Laboratory

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RERF Update Volume 20, Issue 1, 2009

RERF News
versity of Oklahoma Health Sciences Center
Dr. Michael N. Cornforth, Professor and Directorof Biology Division, Department of Radiation
Oncology, University of Texas Medical Branch
Dr. Sally A. Amundson, Associate Professor of
Radiation Oncology, College of Physicians andSurgeons of Columbia University
Special Scientific Councilors
Dr. Gen Suzuki, Chief, Department of Environmen-

As of 30 November 2008, Dr. Yukiko Shimizu
resigned from the position of Assistant Department
Chief, Epidemiology, and was appointed as Part-timeProfessional on 1 December 2008. (See her memories of working at RERF for more than 37 years on
page 13.)
As of 31 December 2008, Dr. Kei Nakachi reachedthe mandatory retirement age and retired from
Department Chief of Radiobiology/Molecular Epidemiology. He was appointed as RERF Consultant
and Project Principal Scientist on 1 January 2009.
Dr. Yoichiro Kusunoki was appointed Acting Chiefof the Department as of 1 January 2009. Dr. Yasuharu
Niwa was recruited and joined the Cell Biology
Laboratory of the Department of Radiobiology/
Molecular Epidemiology on 1 February 2009.
Drs. Mimako Nakano, Research Advisor, and Dr.
Kazuo Ohtaki, Adjunct Specialist (Research Scientist) of Cytogenetics Laboratory, Genetics Department, retired upon expiration of their reappointment
terms as of 31 March 2009. Dr. Yoshiaki Kodama,
Assistant Department Chief of Genetics, wasappointed Acting Chief of the Genetics Department
to replace Dr. Jun-ichi Asakawa as of 1 April.
We have asked Dr. Niwa to write a little about
himself and his interest in the work of RERF.
Yasuharu Niwa
By way of introduction, my name is Yasuharu
Niwa, and I started work at the Department ofRadiobiology/Molecular Epidemiology on February
1 of this year. After graduating from the Graduate
School of the University of Tokushima, I started workat the same university as a research assistant professor. While I was employed there, I traveled overseas
to study at Harvard University, researching mainly
mechanisms behind blood platelet secretion and the

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5
tal Health, National Institute of Public Health(until March, 2009); currently, Professor, Clinic,
International University of Health and Welfare
Dr. Yoshiya Shimada, Team Leader, Experimental
Radiobiology for Children’s Health ResearchGroup, Research Center for Radiation Protection,
National Institute of Radiological Sciences
Dr. Ranajit Chakraborty, Professor and Director,
Center for Genome Information, Department ofEnvironmental Health, University of Cincinnati
College of Medicine

process of differentiationfrom stem cells into blood
platelets. Following thatexperience, I studied epigenetic mechanisms of carcinogenesis based on theexample of liver cancer
as a research scientist at
the Cancer Institute of theJapanese Foundation for
Yasuharu Niwa,
Research Scientist
Cancer Research. After that,
I took up the post of laboratory chief at the National Cardiovascular Center,located in Osaka, where I delved into researchon environmental factors and causative genes inatherosclerosis and hypertension.
I feel that Hiroshima is a really nice city with an
attractive environment, around which I can enjoy
wandering by foot or by taking the streetcars. The
new baseball stadium is completed and is an interesting addition. Hiroshima’s beautiful streets are
symbols of the city’s recovery following the war, andthey symbolize the efforts of the people of Hiroshima
and their strong desire for peace.
Our scientists have uncovered associations
between the atomic bombings and certain diseases.
However, many mechanisms related to the association between radiation exposure and disease development are still unclear, and therefore thoroughanalysis of such mechanisms must be undertaken in
the future. My work at RERF will involve uncovering associations between the bombings and lifestylediseases through the conduct of basic research. I will
be very happy if, based on my prior experience andthe leadership of RERF’s many researchers, I
contribute to the further understanding of suchdisease processes.

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RERF News

Honors and Awards Received by RERF Scientists
We are pleased to informyou that Dr. Nori Nakamura,
RERF Chief Scientist, will
be appointed to serve as amember of Committee 1 ofthe International Commission on Radiological Protection (ICRP) as of 1 July
2009, for a term of four
years.

Nori Nakamura,
Chief Scientist

Receiving “Excellent Poster Presentation”
Award at the 61st General Assembly of
the Hiroshima Medical Association
Ikuno Takahashi, Research Scientist
Department of Clinical Studies, Hiroshima

At the 61st general assembly of the Hiroshima
Medical Association held on November 29–30, 2008,
my report on lifetime risk of stroke, which was basedon a stroke study of Adult Health Study (AHS) subjects, received an award for excellence. The relevant
stroke study started with the unspectacular work ofsingle-mindedly flipping through the medical chartsof a total of 4,500 subjects in order to confirm strokecases. For several months, when I was engaged in
the relevant operations, I had a dream every night
about the medical history charts that I had checked
during the day; however, I also experienced theemotion that I was coming into contact with globallyunique, longitudinal records collected over a halfcentury, an experience that nurtured my desire toreciprocate the contributions made by the large number of health examination participants and ABCCRERF staff members to the continuation of AHS.

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The analysis of a large number of historicallyvaluable records generated the findings that 20–30%
of Japanese people with high blood pressure levels
during middle age had risk of stroke onset and that
this risk was at least twice as high as that for thosewith normal blood pressure. This was the first suchfinding in Japan and could be counted among alimited number of similar results throughout theworld. The study elucidating effects of high bloodpressure levels on stroke onset emphasized the needfor relevant therapies for a large number of asymptomatic patients who have little interest in undergoing lifestyle disease (hypertension) treatment. I
sincerely hope that such epidemiological suggestions
can contribute to rewarding those involved in thecontinuation of the AHS.
In addition, recent major advances in medical
imaging techniques have increased the opportunity
for non-invasive testing. I believe that only RERF
can elucidate whether low-level medical radiation
exposure is harmful to humans, even though radiation is already widelyused in diagnostic
imaging. I will do
my best to elucidate
particularly whether
radiation exposure
promotes the onset ofstroke and other sucharterial sclerotic diseases that affect thequality of subsequent
life and, if so, mechanisms thereof. Everyone’s continued guid- Ikuno Takahashi, Researchance would be greatly Scientist, with her award
appreciated.

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Conference and Workshop Reports

Workshop on Radiation Risk of Breast Cancer
Nori Nakamura, Chief Scientist
The subject workshop was held at the Hiroshima
RERF Auditorium on October 10–11. It was the firstworkshop co-hosted by the National Institute ofRadiological Sciences (NIRS) and RERF. Our
intent was to organize a workshop that would help
the participants readily understand the current
status of research on radiation risk of breast cancer(covering fields from biology to epidemiology).
At the beginning of the workshop, Dr. Jun-ichi
Kurebayashi (Kawasaki Medical University) and Dr.
Yang Xiaohong (U.S. National Institutes of Health)delivered lectures on breast cancer subtypes among
Japanese and Europeans/Americans. Recently, breast
cancer is often classified into about five subtypes,
depending on the expression patterns of several key
genes, including estrogen receptor gene (prognosis
also differs by subtype). In Japan, the backgroundrate of breast cancer overall has been on an upward
trend. However, the fraction of basal-type breast
cancer (subtype with poor prognosis) among theJapanese people still seems to be lower than thatamong Americans and Europeans. Whether all or justsome of the subtypes increase due to radiation
exposure is unknown.
Following the presentations, Dr. Alexander
Borowsky (University of California) delivered alecture on the biology of breast cancer. He explained
what is considered to be the source of differencesamong different pathological types of breast cancer.

Dr. Nobuo Nishi (RERF) summarized epidemiologic
studies of breast cancer among A-bomb survivors,and Dr. Kiyohiko Mabuchi (U.S. National Cancer
Institute) gave an overview of secondary breastcancer risk for patients who had undergone radiation therapy. Thereafter, Dr. Airo Tsubura (Kansai
Medical University) explained biological explanations of factors that are considered in the field of
epidemiology to modify breast-cancer risk. He
suggested that the low breast-cancer risk among those
who experienced their first child-bearing at young
ages might be attributable to differentiation of mammary stem cells. Drs. Mike Atkinson and Soile Tapio(Helmholtz Centre Munich) explained to what extent cancer research technologies have advanced withthe use of paraffin-embedded tissues.
Lastly, Dr. Tatsuhiko Imaoka (NIRS) reported on
results of analysis of gene expression using breastcancer arrays generated by irradiation of rats.
He explained that the gene expression pattern ofradiation-induced breast cancer is different from thatof spontaneous breast cancer. The presentations were
followed by a general discussion session.
Dr. Mabuchi, Dr. Otsura Niwa (NIRS), and I havediscussed possibilities for organizing this workshop
for the past two years or so. Immediately prior to theworkshop, two important international conferenceswere held in Japan. It was a great pleasure for usthat some of the foreign scientists who attended those
conferences also participated in our workshop. Through the workshop sessions, we
keenly realized how much more diverse
than imagined cancer mechanisms are
and how rapidly cancer research has
advanced. The general discussion session
suggested that subtyping of breast cancer
among A-bomb survivors would be aworthwhile project. A number of participants stated that future workshops of thiskind would be indispensable for promotion of comprehensive research on radiation and breast cancer.
On a final note, I would like to express
my sincere appreciation to the staffs of
the Secretariat and the Department of Genetics, who contributed to the convening
Workshop on radiation risk of breast cancer held at the auditorium,of this workshop.
Hiroshima Laboratory

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RERF Update Volume 20, Issue 1, 20098

Conference and Workshop Reports

Radiation Cataractogenesis Workshop
Kazuo Neriishi, Assistant Chief
Department of Clinical Studies, Hiroshima
The Radiation Cataractogenesis Workshop washeld at the RERF auditorium on March 9 and 10,
2009. The following speakers were invited to theworkshop: Drs. Gabriel Chodick (Maccabi
Healthcare Services, Israel), Norman J. Kleiman(Columbia University, USA), Eleanor A. Blakely(Lawrence Berkeley National Laboratory, USA),
Polly Chang (SRI International, USA), Leo T.
Chylack (Harvard Medical School, USA—webconference participation), Francis A. Cucinotta(NASA Johnson Space Center, USA—Dr. Leo T.
Chylack made a presentation on behalf of Dr.
Cucinotta), Atsushi Minamoto (Minamoto Eye
Clinic), Takashi Kitaoka (Nagasaki University),
Takashi Kumagami (Nagasaki University), Yoshiaki
Kiuchi (Hiroshima University), Takashi Kanamoto(Hiroshima University), and Noriko Fujii (Research
Reactor Institute, Kyoto University). Drs. Ohtsura
Niwa, Shin Saigusa, and Shinji Yoshinaga from the
National Institute of Radiological Sciences attended
the workshop as observers.
The objective of the workshop is to elucidate
epidemiological characteristics of radiation cataract
through comparative review of several epidemiological studies, and mechanisms of radiation cataract
development through discussion of molecularbiological studies. Invited participants, who areresearchers engaged in epidemiological studies of
the radiation-exposed (radiologic technologists,
interventional cardiologists, astronauts, Chernobyl

clean-up workers, and A-bomb survivors), engaged
in comparative discussions of their studies of cataract development attributable to low-dose radiation
exposure. Other invited participants, who areresearchers studying molecular biological changes
to the lens (apoptosis protein, crystallin, and ATM
protein) due to radiation, conducted in-depth discussions of their studies of molecular biological changes
due to radiation. By sharing such epidemiologicaland molecular biological information on radiation
cataract, in-depth discussion was carried out to getto the bottom of the matter concerning mechanismsof radiation cataract development.
The following conclusions were obtained:
1. Dose thresholds are probably lower thanthose assumed in the past.
2. In substance, radiation damage to the lenscomprises apoptosis, changes in matrix structure, and crystallin racemization (opticalstructure change of protein).
3. Expression of specific molecular biologicalproteins is involved.
4. Collaborative research should be conductedin the future.
It was proposed to publish the proceedings of thisworkshop in a scientific journal, and the proposal
was approved unanimously. We look forward topresenting scientific highlights from this workshop
in future editions of Update.

Participants of the radiation cataractogenesis workshop

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RERF Update Volume 20, Issue 1, 2009

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Science Article

What and How Large Are the Risks from Prenatal(In Utero) Radiation Exposure?
Roy Shore,1 Misa Imaizumi,2 Yoshimi Tatsukawa,3 Nori Nakamura4
Vice Chairman and Chief of Research, Departments of 2Clinical Studies (Nagasaki)
and 3Clinical Studies (Hiroshima), and 4Chief Scientist, RERF
1Introduction
Since the early publications of the Oxford Studyof Childhood Cancer (OSCC) by Alice Stewart andcolleagues in the 1950s and 1960s, 1 it has been
widely believed that the embryo and fetus areespecially sensitive to the carcinogenic effects ofionizing radiation. The results of their very large casecontrol study (~14,000 childhood cancer deaths, ofwhom ~2,200 received prenatal X ray)2 of in utero
medical diagnostic irradiation and childhood cancers
were largely supported by a number of other casecontrol studies (see Ref. 3). Based on the OSCC
study, an excess absolute risk (EAR) estimate ofabout 6% per Gray (Gy) was derived for childhood
cancer mortality. 4,5 However, the support for aprenatal irradiation effect upon types of childhood
cancer other than leukemia was mixed in various
other studies (e.g., Ref. 6). Furthermore, the several
cohort studies of prenatal radiation exposure lent
weak or no support to a risk of childhood cancer,
although that generalization needs to be qualified bynoting that the cohort studies had limited statisticalpower.3
Childhood Cancer after Prenatal A-bomb Exposure
The atomic-bomb study was rather uninformative regarding prenatal exposure and childhood
cancer, and could be interpreted in different ways.
Jablon and Kato7 reported that only one childhood
cancer was observed before age 10 in the atomicbomb study of 1292 children exposed prenatally,
whereas 0.75 would have been expected from Japanese population baseline rates alone, and from thelower bound of the radiation risk estimate based on
the Stewart study at least 5 excess cancers would
have been expected. The estimated maternal uterine
dose was 1.43 Gy for the only cancer case diagnosedin the prenatal cohort before age 16: a liver cancer atage 6. Delongchamp et al.8 analyzed cancer occurring at ages 16 or under in the cohort and indicated apositive association based on the high dose received
by that cancer case. They indicated that, while thiscase was consistent with the large excess risk duringchildhood suggested by the OSCC study, it was also
compatible with a broad range of risk estimates, andprovided only weak support for the OSCC results.
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Adult Cancer after Prenatal A-bomb Exposure
Given the high estimates of risk of childhood
cancer after prenatal exposure, one might
hypothesize that the adult-cancer risk would be as
great or greater for prenatal exposure than forchildhood exposure. Long-term follow-up of theprenatally exposed cohort of A-bomb survivors has
continued. We are unaware of any other publishedstudy of adult cancer in relation to purely prenatal
radiation exposure, although there is a Techa River
study report on adult cancer among those exposed
both pre- and postnatally. 9 Perhaps due to therelatively low dose distribution in that cohort, thedose response was not significant for either pre- or
postnatal exposure.
The RERF Epidemiology and Statistics
Departments recently reported on the dose-related
incidence of solid cancers over the age range of 12–
55 years among the prenatally exposed A-bombcohort (n = 2,452), compared to the dose-related
incidence among the 15,388 exposed in earlychildhood (ages 0–5).10 A total of 94 solid cancers
was found in the prenatal group and 649 in the larger
childhood irradiated group. The doses reported forthe prenatal cohort in the present summary arematernal uterine doses. Estimates of fetal doses per
se are currently not available, but uterine doses areprobably a reasonable first approximation, sincepreliminary calculations suggested that fetal dosesvary only around 5% from the estimated uterine
doses and also vary relatively little by gestationalage for a given tissue kerma in air.11 In future work,
we hope to derive direct estimates of fetal doses.
There was a dose-dependent excess of cancer
among the prenatal cohort (excess relative rate
[ERR] = 1.0 per Gy, 95% confidence interval [CI]:0.2–2.3), which was fairly comparable to that seenin the childhood-exposed cohort (ERR = 1.7 per Gy,
95% CI: 1.1–2.3). However, when this was examinedon the excess absolute risk (EAR) scale and plottedby attained age, there is a strong suggestion that thetemporal trajectories of risk are different, in that theEAR per 10,000 person-year Gy is rising sharply withage for the childhood-exposure cohort but remains
flat for the prenatal cohort (Figure 1).
The study of solid cancer in adulthood after preRERF Update Volume 20, Issue 1, 2009

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Science Article

Figure 1. Excess relative risk (ERR) and excess absolute risk (EAR) for solid cancers, ages
12–55, among those exposed to the A-bomb in utero or at ages 0–5.
Adapted from Ref. 10.

natal or early-childhood exposure10 had some otherinteresting sidelights. The risk estimates for those
exposed during the first, second, and third trimesters
of fetal development were virtually identical; there
was no evidence for a window of susceptibility bygestational age at exposure. Based on the combined
prenatal and early-childhood exposure cohorts, theradiation EAR was about twice as large for women
as for men (female:male ratio of 2.1, p = 0.02). For
the prenatally exposed, the EAR per 10,000 personyear Gy was 9.2 for females and 4.3 for males.
Leukemia in adulthood is also being examined in
the prenatally-exposed group. In the last completed
analysis through 19928 there were few leukemias toanalyze: 2 in the exposed group and 4 among theunexposed (<0.01 Gy). That analysis indicated thatthe excess leukemia rate in the irradiated group was
marginally significant (p = 0.054), with an excess
rate that was about half as large as, but statisticallycompatible with (p = 0.10), those seen after childhood
exposure. However, there was no dose response, as
the two leukemia cases had estimated doses of only
23 and 40 mGy. An updated analysis is now
underway but is not yet completed.
Experimental studies at RERF have also been
conducted to seek to explain the generally weak ornull findings with regard to cancer risk after prenatal exposure in the A-bomb studies. The Genetics
Department examined chromosome aberrations(translocations) in blood lymphocytes by the Gbanding technique from a group with in utero
A-bomb exposure and by bi-color FISH (fluorescentin situ hybridization) of painting three sets ofchromosomes from their mothers, and found a dose
response for mothers but not for those exposed
prenatally when examined at age 40 years old. This
result was confirmed experimentally by irradiating
pregnant mice and observing the rates of chromosome translocations with bi-color FISH at 20 weeks
of age in both the mothers and the offspring. Those
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studies are described more fully in an earlier Update
article (Nakamura et al., Update 16:7–12, 2005).
More recently, to exclude the possibility that thebone marrow cell pool was derived from a small
number of fetal stem cells, and hence translocation
data from four chromosomes might not have been
representative of the other chromosomes, a wholegenome multicolor FISH (m-FISH) analysis wasapplied to the same samples of mice; this confirmed
the lack of dose response for the prenatally exposed
mice (Nakano et al., manuscript in preparation).
However, new preliminary data suggest for epithelial cells there may be a dose response after prenatal
exposure, unlike for lymphocytes, so the story is still
evolving.
Thyroid Disease after Prenatal A-bomb Exposure
Since so little is known about the effects inadulthood of prenatal radiation exposure, it seemed
important to examine other health outcomes besides
cancer. The prevalence of thyroid nodular disease
was examined, since the thyroid gland is one of themost radiosensitive sites, especially among those
who are young at exposure.12 It was possible in the
Hiroshima and Nagasaki Adult Health Study (AHS)
to screen 319 prenatally-exposed persons with known
doses about 55–58 years after exposure. The meanuterine dose in the exposed group (≥5 mGy) was
about 0.26 Gy (range of 0.02 to 1.79 Gy). For
comparison to the prenatally exposed cohort, thyroid
nodule prevalence also was examined among the 437
examined individuals who were ages 0–5 years at
exposure; the mean dose in that exposed group wasmuch higher, 0.92 Gy, because for postnatal AHS
study subjects it was possible to enrich the samplingof higher-dose persons.
As shown in Figure 2, Dr. Imaizumi and colleagues13 found an apparent increase in the risk ofsolid thyroid nodules (odds ratio [OR] at 1 Gy = 2.78,
95% CI: 0.5, 12) although the radiation risk was not
RERF Update Volume 20, Issue 1, 2009

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Science Article

Figure 2. Risk of solid thyroid nodules by radiation dose for the in utero-exposed
clinical cohort. Adapted from Ref. 13.

statistically significant, probably owing to the limited
statistical power due to the relatively small sample
size and low dose distribution. However, this risk
estimate was similar to the study’s estimate for childhood exposures (OR at 1 Gy = 2.65, 95% CI: 2.0–
3.7). An examination of thyroid nodule risk in theprenatal cohort did not show any differences by
gestational week of exposure.
They also evaluated the prevalence of autoimmune thyroid disease in the prenatally exposedcohort. No dose-related associations were found fortests of antithyroid antibodies, antithyroid-antibody
negative or positive hypothyroidism, or Graves’disease. Nor did they show any differences in dose
response by gestational week at exposure. The
findings regarding autoimmune thyroid disease were
not surprising, since the results have been null in the
AHS study, too.12
Circulatory Disease after Prenatal A-bomb
Exposure
The other set of health outcomes examined in the
AHS prenatal cohort are circulatory diseases andconditions, because mortality from circulatory
diseases shows an association with radiation

exposure in the epidemiologic Life Span Study(LSS). The incidence rates of primary hypertension,
hypercholesterolemia, stroke, and myocardial
infarction were examined in relation to radiation doseamong the AHS participants between 1978 and 2003
by Dr. Tatsukawa and colleagues.14 Because thenumbers of strokes and myocardial infarctions wereso small, they were combined for analysis. These
conditions were considered positive when AHS clinic
measurements or assessments met standard defined
criteria, or when there was a relevant confirmed
diagnosis or prescription by another physician. For
comparison, the dose-related incidence of these
conditions was examined in parallel fashion for thosein the AHS who were ages 0–9 years at exposure.
There were 506 prenatally exposed AHS subjects and1,053 exposed at ages 0–9.
Because a series of lifestyle-related factors
besides radiation impact the risk of circulatory
diseases, smoking, alcohol consumption, andobesity (body mass index) were included in the analyses. The risk estimates for the cohorts with prenatal
and childhood exposure are shown in the Table. For
hypertension and hypercholesterolemia the radiation
risk estimates for the prenatal and childhood cohorts

Table. Dose-related (RR at 1 Gy) risk of incident circulatory diseases or conditions for the prenatally- andchildhood-exposed cohorts in the AHS
Prenatally-exposed cohort

Childhood-exposed cohort

RR (95% CI)

P-value; No. cases

RR (95% CI)

Hypertension

1.20 (0.6–2.4)

0.60; n = 155

1.15 (1.0–1.3)

Hypercholesterolemia

1.33 (0.7–2.4)

0.35; n = 223

Nonfatal CVD*

0.09 (<0.01–80)

0.49; n =6

Fatal+nonfatal CVD*

3.94 (0.8–20)

0.10; n =9

OutcomeP-value; No. cases
0.06;

n = 318

1.05 (0.9–1.2)

0.45;

n = 508

1.72 (1.2–2.4)<0.001; n = 37

1.76 (1.3–2.4)<0.001; n = 48

* CVD (cardiovascular disease) here combines stroke and myocardial infarction. Adapted from Ref. 14

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RERF Update Volume 20, Issue 1, 2009

12

Science Article
are similar. For nonfatal stroke and myocardial
infarction combined (labeled cardiovascular disease[CVD]), there was no apparent association for the
prenatal cohort for nonfatal disease, although a dosedependent risk was seen in the childhood-exposedcohort. However, when both fatal and nonfatal CVD
were examined together, there appeared to be aradiation-related risk, though it did not quite attainstatistical significance. The instability of the purely
nonfatal vs. the nonfatal plus fatal CVD risk
estimates clearly indicates that longer follow-up witha larger number of CVD diagnoses is needed toprovide a more precise assessment. Again, statistical power was the principal limitation in examining
the prenatally exposed cohort, but we conclude thatthe radiation-associated risks appear reasonably
similar for the prenatal and childhood cohorts.
To summarize, the ABCC-RERF data provide
weak or no support for a large childhood cancer risk
from prenatal radiation exposure as has been reportedby the OSCC and other smaller case-control studiesof medical diagnostic irradiation during pregnancy.
However, the statistical power to assess childhood
cancer risk in the LSS was limited. A major concern

by the radiation risk assessment community has beenthat the large radiation risks for childhood cancer
reported by the OSCC would continue on into adulthood, such that the lifetime cancer risk would beappreciably larger than that for childhood radiation
exposure. This does not appear to be the case—therisk from prenatal exposure may even be smaller thanthat for early childhood exposure for solid cancers,
though it is too early to reach a firm conclusion. For
thyroid nodules the radiation risks from prenatal andchildhood exposure are similar. For hypertension andcirculatory diseases (stroke and myocardial infarction), again the radiation dose-dependent risks arecomparable for prenatal and childhood exposures.
In conclusion, the prenatally exposed cohort
of atomic-bomb survivors appear to represent a sensitive population. It is unclear whether their degreeof risk is as great as that for the early-childhood exposed cohort, although the two sets of risk estimatesare broadly compatible. Since the prenatal cohort isentering the age period for the maximum expressionof adult-onset diseases, the next one to three decadesof follow-up will provide unique and valuable data.

References
1. Stewart A, Webb J, Hewitt D. A survey of childhood malignancies. Br Med J 1:1495-508, 1958.
2. Gilman E, Kneale G, Knox E, et al. Pregnancy x-rays and childhood cancers: Effects of exposure age andradiation dose. J Radiol Protect 8:3-8, 1988.
3. International Commission on Radiological Protection (ICRP). Biological Effects after Prenatal Irradiation(Embryo and Fetus). Oxford, UK: International Commission on Radiological Protection (Pergamon Press);
2003.
4. Muirhead C, Kneale G. Prenatal irradiation and childhood cancer. J Radiol Prot 9:209-12, 1989.
5. Doll R, Wakeford R. Risk of childhood cancer from fetal irradiation. Br J Radiol 70:130-9, 1997.
6. MacMahon B. Prenatal x-ray exposure and childhood cancer. J Natl Cancer Inst 28:1173-91, 1962.
7. Jablon S, Kato H. Childhood cancer in relation to prenatal exposure to atomic-bomb radiation. Lancet 2:10003, 1970.
8. Delongchamp RR, Mabuchi K, Yoshimoto Y, et al. Cancer mortality among atomic bomb survivors exposed inutero or as young children, October 1950–May 1992. Radiat Res 147:385-95, 1997.
9. Ostroumova E, Akleyev A, Hall P. Infant mortality among offspring of individuals living in the radioactively
contaminated Techa River area, southern Urals. Acta Medica Nagasakiensia 50(1):23-8, 2005.
10. Preston DL, Cullings H, Suyama A, et al. Solid cancer incidence in atomic bomb survivors exposed in utero or
as young children. J Natl Cancer Inst 100:428-36, 2008.
11. Kerr GD. Organ dose estimates for the Japanese atomic bomb survivors. Health Phys 37:487-508, 1979.
12. Imaizumi M, Usa T, Tominaga T, et al. Radiation-dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic-bomb survivors 55–58 years after radiation exposure. JAMA 295:1011-22, 2006.
13. Imaizumi M, Ashizawa K, Neriishi K, et al. Thyroid diseases in atomic bomb survivors exposed in utero. J Clin
Endocr Metab 93:1641-8, 2008.
14. Tatsukawa Y, Nakashima E, Yamada M, et al. Cardiovascular disease risk among atomic bomb survivors exposed
in utero, 1978–2003. Radiat Res 170:269-74, 2008.

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RERF Update Volume 20, Issue 1, 2009

13

Human Interest Notes

Taking Early Retirement
Yukiko Shimizu, Part-time Professional
Department of Epidemiology, Hiroshima

I decided to take early retirement last November,but have continued to stay at RERF for some time asa part-time professional in the Department of
Epidemiology. Your continued support and guidance
would be appreciated.
At the end of 1972 when I was a student at the
Department of Mathematics, Faculty of Science,
Hiroshima University, my seminar professor, Dr.
Sumiyasu Yamamoto, recommended that I interview
with the Atomic Bomb Casualty Commission(ABCC, RERF’s predecessor). After an interview
with Dr. Iwao Moriyama, Chief of the Departmentof Statistics at that time who also happens to be theuncle of the famous singer Ryoko Moriyama, I joined
the Department of Statistics at ABCC in April 1973.
Then, in July of the same year, Dr. Gilbert Beebe
assumed the position of Statistics Department Chief.
The attached photograph shows the researchscientists of the department at that time.
The Department of Statistics in those days
included the present-day departments of Epidemiology, Statistics, Information Technology, and partof the Clinical Studies Department (Clinical
Administration Section, etc.), comprising two-thirdsof all ABCC employees. With no personal computers
installed in individual offices at that time, two
researchers had to share one office. My officemate
was Dr. Charles Land, who collaborates with RERF
scientists and still visits RERF occasionally, and weapparently were able to get our messages across toeach other, speaking a mixture of English and Japanese.

I am amazed at how
fast the 36 years havepassed since then.
They say that it isfortunate to be blessedwith good teachersand superiors when
you are young, andthat is exactly thecase with me. I owe
my many years of
devotion to epidemiological research
to Dr. Hiroo Kato,
Yukiko Shimizu in her
who taught me thepresent office
field of epidemiology
from my entry level. In those hectic days, wheneverI asked him the deadline of the work he hadrequested, he would reply, “by yesterday.” Dr.
Shoichiro Fujita, who always used to shout at me,with warm-heartedness behind his sharp words,
taught me statistical techniques. Mr. Tetsuo Imadaand Ms. Kyoko Katagami, from the Computer
Section (today’s Department of Information Technology), taught me about actual data. They grew tiredof how I always bombarded them with questions,and finally bestowed upon me the nickname “Yuki,
the soft-shelled turtle” (based on the idea that suchturtles refuse to let go once they sink their teeth into
something, imagery that connotes persistence), but
I remember they always taught me kindly. I consider
myself very lucky to have had such strict but warmhearted superiors. I also was blessed by talented
subordinates, who provided me with the latest
information and helped with my research. In addition, I was able to learn state-of-the-art statisticalmethods still unknown in Japan from non-Japanese
research scientists.
On the occasion of my retirement, I would like toexpress my deepest appreciation to such kindsuperiors and capable subordinates, those mentioned
here, and all other RERF members, for their support.
Retiring two years earlier than mandatory retirement,
I would like to make good use of that time taking
care of my elderly parents.

Staff of the ABCC Statistics Department in 1973

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RERF Update Volume 20, Issue 1, 2009

14

Human Interest Notes

Recontacting Work
Toshiko Tsukamoto
Former Recontactor, Hiroshima

About five US military Quonset-hut buildings
were located in Hijiyama Park at the top of a small
hill in Minami Ward, Hiroshima City. In Japan, I had
never seen such structures, which looked likeelementary or junior high-school buildings. Although
there were no job listings in newspapers, my motherin-law heard from somebody that they were looking
for workers and told me to go there. If memory serves
me correctly, that was in July 1957. I was told to be
there by 8:30. I walked up the hill, entered thebuilding from the front entrance and, following thesigns on the walls, went upstairs to the auditorium.
Surprisingly, half of the seats were already occupied.
After we waited for about 15 minutes, a tall woman,
who looked to be older than I was, came in and said,“I am the supervisor of the reception unit. I will now
explain the work we do here. Today 165 people havegathered together. Thank you for coming. Six men
and six women among you will be hired by thefoundation after taking written exams for four days
and undergoing a chest X-ray exam on the fifth day.”
About one-and-a-half months after managing topass the written test, I finally received notice that I
had been accepted. Starting in September of that year,
my busy days began, as my job started at 8:30. I got
up at 5:00 in the morning, prepared breakfast, left
home at 7:30, took a bus and a streetcar, and walked
up Hijiyama Hill. Though I was busy, I was full ofyouth and energy, and was intensely involved in thework like a tireless child. I worked thusly for 23 years
until my mandatory retirement age.
Let me tell you about some of the impressive
contacting work I did during that time. Out of 30
contactors, about five were men. There were as many

Jeeps used for contacting work around 1949

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jeeps and drivers as contacters. Drivers got on theleft side of the jeeps because the steering wheels wereon that side, and we contacters rode on the right side,which had no door. Without holding onto the leather
ring hanging from the ceiling, we would have been
thrown from the vehicle. Although the work was hardon rainy or snowy days, we contactors did our best
to overcome such difficulties. Finding houses was
not as easy as it is now. Address numbers were notsequential, and sometimes we had to run around tofind the right houses. Once I had a card with theaddress of a professor, but I later found that his
residence was in an old wooden apartment building.
I first was looking for a nice big house because his
occupation indicated “university professor.”
Sometimes, a card indicated that the person I waslooking for was a mobster (yakuza) boss. I once went
to the house of a yakuza boss in a certain town that
had a gorgeous gate. After I rang the doorbell, fiveor six young men in black suits appeared and grunted“Hey!” My unit supervisor had told me a cautionary
tale of the time he visited a yakuza boss near a certain
train station and was chased away by someone witha kitchen knife, who shouted, ‘I hate ABCC. Go
away.’ My heart fluttered, but I spoke to them with acalm expression. Two dogs also appeared. The big
dogs were Great Danes. They approached me,
growling. I had a Spitz breed at home, but these dogs
were three times as big. Telling myself that if I ran, I
would be the loser, and recognizing that such asituation was part of my job, I approached the dogs,
saying “Good boys, good boys…” One of themsuddenly stood on his back legs, and put one paw on
my shoulder, peering into my eyes. I looked back at
him and smiled. When one of the young men in a
black suit called the dog’s name, pulled on his collar
and put him down on the ground, the yakuza boss
appeared and said, “What’s the matter?” He was asmall man of ordinary appearance. I gave him myname card and desperately explained the purpose of
my visit. “Aren’t you afraid of dogs?” he asked. I
said, “No. I love dogs and cats. I have a small dog at
home.” Then he said, “My dog probably smelled yourdog on you. If you’d have run, he would have chasedyou.”
He then turned and called to his wife, who wasinside the house, and told her to take me to the livingroom and listen to my explanation. I was taken to abeautifully decorated room, and was served black
tea. After we talked, I was able to make an appointRERF Update Volume 20, Issue 1, 2009

Human Interest Notes
ment for a health examination. It was also agreed
that the boss would undergo health examinations
every two years. Our driver, who was waiting in thejeep, said, “I was worried about you. You made an
appointment with a yakuza—wow!” Even yakuza arehuman beings and Japanese. I learned that if you arepolite to them, they will be polite to you.
After about 10 years of such service, during which
the unit supervisor, the section chief, and thedepartment chief positions were each replaced twice,
my bosses said, “Mrs. Tsukamoto, you are good atmaking appointments, so please take charge ofrecontacting work.” And that is how I started
recontacting work. I reviewed cards indicating thatthe first contact had been refused. I never started out
by asking these people to come for an examination.
Instead, I asked them, “Why do you dislike ABCC
(or RERF) so much?” As I asked these people
questions one by one, they talked about their various
experiences. I used to listen to them, imagining
how I would have felt if I had been them. Somepeople, with tears in their eyes, talked about the deathof their parents, children, brothers, sisters, or
grandparents due to the atomic bombing.
When the bomb was dropped, I was living withmy mother and my younger sister, both of whomwere outside the house. My mother died that day,August 6. My sister (21 years old then) suffered burns
on 90% of her body, vomited blood, and excreted
bodily waste without any control. In spite of mydesperate attempts at nursing, she died on August
16. I was left alone, and spent a long time crying
everyday. I thought of hanging myself from a tree inthe garden of my house, but decided to live, tellingmyself that I was the only one who could protect myfamily grave. I told about my experiences to somecandidate health examinees, and sometimes we cried
together hand in hand. Once I was talking to a woman
who was about 30 years older than I and had refused
to undergo any examinations. While talking, I had
tears in my eyes because she looked like my mother.
Then she hugged me, and we cried together. With
that, she agreed to come to the foundation for healthexaminations.
Some people refused to come for examinations

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15
because they believed that 1) ABCC was collecting
a large amount of blood from each examinee to mix
it together and sell it, or 2) ABCC diagnosed even
healthy people with this and that illness, did notprovide any medicine, and referred them to university
hospitals, which paid gratuity to ABCC in return. I
gave detailed explanations on both of these issues,and such misunderstandings were thereby resolved.
Because I listened intently to their stories, they
eventually opened their minds, and about seven often people who had initially refused agreed to makeappointments. I cannot explain why exactly thishappened. One of those people, a woman about five
years older than I was, once said to me, “I was waiting
for you because I knew that it was time for you tocome soon.” On such occasions, I felt happy about
my work. One of the contactors asked me, “Mrs.
Tsukamoto, don’t you ever feel frustrated with thiswork? Aren’t you fed up with it?” I responded that I
actually enjoyed the work, but she replied, “I can’t
understand why.” Once one of the contactors asked
me, “Do you use hypnosis or something?” and I
answered, “No, I don’t, because I know nothing about
it.”
Fifty years have passed since I joined ABCC.
Around then, one of the foreign doctors said thatthough he had heard Japan was an advanced country,
he thought the Japanese were 30 years behind interms of taking care of their own health. Nowadays,
many people willingly apply for complete medical
checkups or undergo health examinations in mobile
screening buses that visit cities, towns, or villages.
Preventive medicine has certainly made great strides.
However, no matter the era in which we live, it isimportant for human beings to have strong determination to follow good examples and refuse to engage
in harmful behaviors. Animals, such as dogs and cats,
have to be told repeatedly what is right and what iswrong. It might be my prejudice, but I have heardthat only humans have “shame” and “conscience”
and use these two emotions as standards for making
judgments. Along these lines, I believe it is importantfor human beings to think carefully and question
ourselves.

RERF Update Volume 20, Issue 1, 2009

16

Human Interest Notes

In Memoriam
Thelma and Judith Jablon
Twice we were saddened to learn that family
members of one of ABCC’s most distinguished scientific leaders died. Thelma Jablon died January 16,
2009, at the age of 89 at her home in Bethesda, Maryland. She was the wife for 67 years of the scientist
who had a major role in designing and implementing the early important ABCC study cohorts, Seymour
Jablon. Mrs. Jablon was a teacher for most of herlife and lived with her husband in Japan from 1960–
1963 and from 1968–1971 where she taught at aninternational school and became a connoisseur ofJapanese art. One of the daughters of Thelma andSeymour Jablon, Judith Jablon, died in Bethesda,
May 10, 2009.

Takashi Takemoto
We received wordt h a t D r. Ta k a s h i
Takemoto died on
January 2, 2009, atthe age of 83. Heworked for the Department of Genetics
in the early period of
the ABCC, 1950–
1954. Dr. Takemoto
Takashi Takemotoentered Hiroshimaaround 1950
the morning after thebombing after arriving from Okayama Medical
University in Okayama City where he had been
staying. In an interview about the ABCC in the
Chugoku Shimbun (7 June, 2007), Dr. Takemoto
discussed his first work at ABCC which was to study
newborn infants. He and others made door-to-door
visits to homes in which a baby was born, based on
cards on which addresses had been typed. In order
to eliminate prejudice and bias, the examiners did
not know whether the parents were A-bomb survivors or not. They examined the babies to note if they
had congenital anomalies, and upon leaving thehomes, gave soap to the mothers that was made in
the U.S.
Over the years, some people have been critical of
the fact that ABCC conducted examinations but did

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Seymour (right) and Thelma (left) Jablon with the
Health and Welfare Minister Juro Saito in his office in1987

not provide medical treatments. Dr. Takemoto wasvery upset with the article with his interview thatwas printed in the newspaper because “nothing waswritten about ABCC’s great contribution to medicalcare in Hiroshima, and its cooperation with medicalorganizations in the city.” He explained to thereporter and to RERF in a letter that it was quite
natural that ABCC did not provide medical treatment
because “the nature of ABCC was not to competewith other medical organizations in the city ofHiroshima.”
After resigning from ABCC, Dr. Takemoto was
employed as a hospital doctor by the Department ofOtorhinolaryngology at Hiroshima City Hospital. He
pointed out that all of the histopathological tests atthe city hospital depended on ABCC. In addition,
personnel exchanges between the Departments of
Pathology at ABCC and Hiroshima University
resulted in fruitful results. Because of the good
relationship between the two organizations, private
practitioners were able to receive reliable test reports.
Also, there was very little non-Japanese literature in
medical libraries in Japan during the war, but there
was a large volume of U.S. and a small amount of
U.K. literature stored at ABCC’s library which wasmade available to Japanese physicians. ABCC
apparently provided photocopies of articles and lentvarious books to physicians free of charge.

RERF Update Volume 20, Issue 1, 2009

Facts and Figures

17

RERF Research: Themes, Prioritization, 5-year Program
Goals, Interdepartmental Programs, and a New Contract
with the U.S. National Cancer Institute
Roy Shore, Vice Chairman and Chief of Research
The 36th Scientific Council Report indicated that
Scientific Councilors were pleased with the 5-year
program goals that were developed by RERF toprovide a road map for establishing research
priorities, allocating resources, and setting research
project timelines. RERF leadership has worked
interactively with the departments to accomplish thisand to develop a working set of priorities for existing
research projects. We have identified major research
themes and have begun working on mechanisms toallocate resources, and to set and review project
milestones and timelines.
The Scientific Councilors were also pleased thatinterdepartmental committees or working groups
have been established for programs related to
cardiovascular disease (chair: Dr. Roy Shore),children of A-bomb survivors (F1 studies) (chair:
Dr. Kazunori Kodama), and dosimetry (chair:
Dr. Toshiteru Okubo). We expect additional interdisciplinary working groups will be developed forcataract studies, the genetics of various types ofcancer, and immunological studies.
To further communication, monthly colloquia
are held for all RERF research scientists, and departments have “work in progress” presentations every
one or two weeks that usually include members of otherdepartments and research leaders. Other approaches
to enhance productivity and collaborative interactions among RERF scientists are being considered,including the establishment of shared core facilities,
centralization and integration of the management of
databases and biosamples, and facilitation of international collaborations. Stay tuned and we will keep
you informed as those plans develop.
In September 2008, RERF scientists prepared aresearch proposal in response to a Request for
Proposal (RFP) titled “Support for EpidemiologicalStudies of Cancer Among Atomic-bomb Survivors”
that was issued by the U.S. National Cancer Institute(NCI). RERF was notified that the proposal was
evaluated and was found to be acceptable and acontract was awarded with funding in December
2008. The contract is approximately $300,000 per
year for a period of five years and is a continuationof a long-term collaboration between RERF and theRadiation Epidemiology Branch of the NCI that goesback to 1979. The original project was supported
by means of a prime contract between the NCI
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and the National
Academy of Sciences (NAS) witha subcontract between NAS and
RERF. The newcontract will provide funding directly to RERF
and the project
co-directors are
Kazunori Kodama
Roy Shore, Vice Chairman(RERF Chief Sciand Chief of Research
entist) and Roy
Shore (RERF Vice Chairman and Chief of Research).
The contract will focus on enabling NCI scientists to work with RERF research scientists to analyze
data and prepare reports on cancer incidence risks
that are associated with the Life Span Study (LSS)
cohort. Some of the projects include: completion ofa series of reports on cancer incidence in the in utero
cohort and the subset of the LSS that includes people
exposed in early childhood (see review of thesestudies on page 9 of this issue of Update); updated
analyses of radiation effects on lympho-hematopoietic malignancies (leukemia, lymphoma, andmultiple myeloma); lung cancer incidence; and othermutually agreed upon projects that might be developed during the term of the contract.
The past support from the NCI has enabled thetumor registries in Hiroshima and Nagasaki to bestrengthened and the solid tumor data has been
recently updated an additional 11 years through 1998
(Preston et al., Radiation Research 168:1-64, 2007).
The updated report evaluated risks for total solidcancers and for 18 specific tumor sites plus a residual
category. More detailed analysis of the residual
category identified, for the first time, urothelial cell
cancer as a radiation-related cancer type. Multidisciplinary studies will involve the acquisition anduse of biological materials and mail surveys will be
used to provide valuable information on risk factorsthat is not available from routine mortality and cancer
incidence follow-up of the LSS cohort. Finally, casecontrol studies will continue to explore whether
changes in blood nutrient, hormone, or antibody
levels pre-diagnosis correlate with the risk of cancer
for selected sites.
RERF Update Volume 20, Issue 1, 2009

18

Research Protocols and Recent Publications

Research Protocol Approved in
October 2008–March 2009

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

RP 6-08 Liver Stiffness Study Using Elastometer in Hiroshima Atomic-bomb Survivors
Ohishi W, Tatsukawa Y, Fujiwara S, Hsu WL, Kohata
M, Yamada M, Nishi N, Tsuge M, Chayama K
During two examination cycles (four years), we
will measure liver stiffness as a marker of liver
fibrosis severity with an elastometer for about 3,800
participants of the Adult Health Study (AHS)(including the expanded group of younger survivors)
in Hiroshima to examine the relationship between
liver stiffness and radiation exposure. In analyzing
liver stiffness, we will evaluate possible confounding
factors, such as biomarkers related to chronic
inflammation, insulin resistance and others, bodymass index (BMI), alcohol intake, diet, and hepatitis
virus infection. We will also examine the involvement of liver stiffness in the prevalence of atherosclerotic disease.

Aragane NS, Imai K, Komiya K, Sato A, Tomimasu
R, Hisatomi T, Sakuragi T, Mitsuoka M, Hayashi
S, Nakachi K, Sueoka E. Exon 19 of EGFR mutation in relation to the CA-repeat polymorphism in
intron 1. Cancer Science 2008 (June); 99(6):11807.
Asia Pacific Cohort Studies Collaboration (RERF:
Nakachi K). Cigarette smoking, systolic bloodpressure, and cardiovascular diseases in the AsiaPacific region. Stroke 2008; 39(6):1694-702.
Fukuzawa M, Yamaguchi R, Hide I, Chen Z, Hirai
Y, Sugimoto A, Yasuhara T, Nakata Y. Possible
involvement of long chain fatty acids in the sporesof Ganoderma Iucidum (Reishi Houshi) to its antitumor activity. Biological and Pharmaceutical
Bulletin 2008 (October); 31(10):1933-7.
Hagino H, Furukawa K, Fujiwara S, Okano T,
Katagiri H, Yamamoto K, Teshima R. Recent
trends in the incidence and lifetime risk of hip fracture in Tottori, Japan. Osteoporosis International
2009 (April); 20(4):543-8.
Hamatani K, Eguchi H, Cologne JB, Soda M, Abe
K, Hayashi T, Nakashima M, Sekine I, Hayashi Y,
Nakachi K. Gene alterations preferentially occurredin papillary thyroid cancer among atomic bomb
survivors. Nagasaki Igakkai Zasshi [Nagasaki
Medical Journal] 2008 (September 25); 83(Special
issue):264-7. (Proceedings of the 49th Late
A-bomb Effects Research Meeting, 2008) (Japanese)
Haruta D, Matsuo K, Ichimaru S, Soda M, Hida A,
Sera N, Imaizumi M, Nakashima E, Seto S,
Akahoshi M. Men with Brugada-like electrocardiogram have higher risk of prostate cancer.
Circulation Journal 2009 (January); 73(1):63-8.
(RERF Report 3-08)
Katayama H. How the personal information is protected in the cancer registry. JACR Monograph2008 (March); No.13:35-9. (Japanese)
Katayama H, Tatsukawa Y, Sakata R. Report on aquestionnaire to atomic bomb survivors in Hiroshima
and Nagasaki who emigrated to Brazil. Nagasaki
Igakkai Zasshi [Nagasaki Medical Journal] 2008
(September 25); 83(Special issue):301-3. (Proceedings of the 49th Late A-bomb Effects Research
Meeting, 2008) (Japanese)
Kodaira M, Ryo H, Takahashi N, Kamada N,

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RERF Update Volume 20, Issue 1, 2009

19

Recent Publications
Furukawa K, Nakajima H, Nomura T, Nakamura
N. Screening for microsatellite mutations in thechildren of A-bomb survivors. Nagasaki Igakkai
Zasshi [Nagasaki Medical Journal] 2008 (September25); 83(Special issue):345-8. (Proceedings of the49th Late A-bomb Effects Research Meeting,2008) (Japanese)
Nakanishi S, Yamane K, Ohishi W, Nakashima R,
Yoneda M, Nojima H, Watanabe H, Kohno N.
Manganese superoxide dismutase Ala16Val polymorphism is associated with the development oftype 2 diabetes in Japanese-Americans. Diabetes
Research and Clinical Practice 2008 (September);81(3):381-5.
Nakashima E, Neriishi K, Akahoshi M, Preston DL.
Postoperative cataract incidence in Hiroshima
atomic-bomb survivors 1986–2006: A preliminary
analysis. Nagasaki Igakkai Zasshi [Nagasaki
Medical Journal] 2008 (September 25); 83(Special
issue):243-7. (Proceedings of the 49th Late
A-bomb Effects Research Meeting, 2008) (Japanese)
Nishi N. Multilevel analysis of socioeconomic factors. Kawakami N, Kobayashi Y, Hashimoto H,
ed. Health and Social Disparity—Japan and Beyond. Melbourne: Trans Pacific Press; 2009
(March), pp 211-39.
Noda A, Hirai Y, Kodama Y, Nakamura N. Implications of radiation-induced tandem repeat instability. Hoshasen Seibutsu Kenkyu [Radiation Biology Research Communications] 2008 (June);
43(2):107-18. (Japanese)
Ohara M, Hayashi T, Kusunoki Y, Nakachi K,
Fujiwara T, Komatsuzawa H, Sugai M. Cytolethal
distending toxin induces caspase-dependent and-independent cell death in MOLT-4 cells. Infection and Immunity 2008 (October); 76(10):478391.
Ohishi W, Chayama K. Therapy for chronic hepatitis B. Medical Practice 2008 (October); 25(10):1847-51. (Japanese)
Ozasa K. Integrated analyses of three large-scalecommunity-based cohort studies conducted in
1990s. Biomedicine and Therapeutics 2009
(February 10); 43(2):11-3. (Japanese)
Santen RJ, Song RX, Masamura S, Yue W, Fan P,
Sogon T, Hayashi SI, Nakachi K, Eguchi H.
Adaptation to estradiol deprivation causes up-regulation of growth factor pathways and hypersensitivity to estradiol in breast cancer cells. Advances
in Experimental Medicine and Biology 2008;
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630:19-34.
Sigurdson AJ, Ha M, Hauptmann M, Bhatti P, Sram
RJ, Beskid O, Tawn EJ, Whitehouse CA, Lindholm
C, Nakano M, Kodama Y, Nakamura N, et al. International study of factors affecting human chromosome translocations. Mutation Research 2008
(April 30); 652(2):112-21.
Suganuma M, Yamaguchi K, Ono Y, Matsumoto H,
Hayashi T, Ogawa T, Imai K, Kuzuhara T,
Nishizono A, Fujiki H. TNF-α-inducing protein,a carcinogenic factor secreted from H. pylori, enters gastric cancer cells. International Journal ofCancer 2008; 123(1):117-22.
Suyama A. Shoud we conduct the population-based
prostate cancer screening? The 15th Tokyo Prostate Cancer Forum. Tokyo: Reno.Medical K.K.
2009 (February), 2-28. (Japanese)
Suyama A, Izumi S, Koyama K, Sakata R, Nishi N,
Soda M, Grant EJ, Shimizu Y, Furukawa K,
Cullings HM, Kasagi F, Kodama K. The offspringof atomic bomb survivors: Cancer and non-cancer mortality and cancer incidence. Nakashima M,
Takamura N, Tsukasaki K, Nagayama Y,
Yamashita S, eds. Radiation Health Risk Sciences:
Proceedings of the First International Symposiumof the Nagasaki University Global COE Program“Global Strategic Center for Radiation Health Risk
Control.” 2008 (December), pp 57-62.
Suyama A, Soda M. The current status of cancer registries in Nagasaki Prefecture. JACR Monograph2009 (March); No.14:35-8. (Japanese)
Tamakoshi A, Nakachi K, Ito Y, Lin Y, Yagyu K,
Kikuchi S, Watanabe Y, Inaba Y, Tajima K. Soluble
Fas level and cancer mortality: Findings from anested case-control study within a large-scale prospective study. International Journal of Cancer
2008; 123(8):1913-6.
Tatsukawa Y, Hsu WL, Yamada M, Akahoshi M,
Fujiwara S. Elevated neutrophil count and hypertension. Ketsuatsu [Journal of Blood Pressure]2009 (March); 16(3):6-7. (Japanese)
Tsuge M, Noguchi C, Hiraga N, Mori N, Hiramatsu
A, Imamura M, Ohishi W, Arataki K, Aikata H,
Kawakami Y, Takahashi S, Chayama K. A case offulminant hepatic failure caused by hepatitis E
virus. Clinical Journal of Gastroenterology 2008
(June); 1(2):69-74.
Ueno T, Soma M, Tabara Y, Tokunaga K, Tahira K,
Fukuda N, Matsumoto K, Nakayama T, Katsuya
RERF Update Volume 20, Issue 1, 2009

20

Recent Publications
T, Ogihara T, Makita Y, Hata A, Yamada M,
Takahashi N, Hirawa N, Umemura S, Miki T.
Association between fatty acid binding protein 3
gene variants and essential hypertension inhumans. American Journal of Hypertension 2008
(June); 21(6):691-5.
Yoshida K, Hayashi T, Morishita Y, Nagamura H,
Maki M, Sora M, Imai K, Kusunoki Y, Nakachi
K. Genetic factors underlying risks of radiationassociated cancers. Nagasaki Igakkai Zasshi[Nagasaki Medical Journal] 2008 (September 25);
83(Special issue):254-8. (Proceedings of the 49th
Late A-bomb Effects Research Meeting, 2008)(Japanese)

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Publications Using RERF Data
The following publications represent research done
by non-RERF scientists based on the data publicly
available from RERF.
Little MP. Leukemia following childhood radiation
exposure in the Japanese atomic bomb survivors
and in medically exposed groups. Radiation
Protection Dosimetry 2008; 132(2):156-65.
Richardson DB. Exposure to ionizing radiation in
adulthood and thyroid cancer incidence. Epidemiology 2009 (March); 20(2):181-7.

RERF Update Volume 20, Issue 1, 2009