Children of Atomic-bomb Survivors (F1) Study
Whether radiation-related genetic abnormalities--if they exist--translate
into birth defects or health effects is the focus of health studies on
the first generation (F1)
of offspring of the survivors.
Mortality and cancer incidence
RERF is monitoring causes of death and occurrence of cancer in a
cohort of about 77,000 persons who were born to atomic-bomb survivors
between May 1946 (i.e., children conceived after the time of their
parents' atomic-bomb radiation exposure) and 1984. The methods of
monitoring are the same as with the Life
Span Study cohort (tracking of deaths through the family registration
system and identification of cancer diagnoses through local cancer
registries). In view of the relatively young ages of cohort members,
continued follow-up is required before we can reach any conclusions
regarding the genetic effects of atomic-bomb radiation exposure
on the rate of death or cancer incidence.
F1 Mail Survey and
F1 Clinical Study
A joint effort between the Epidemiology and Clinical Studies Departments,
this study began in 2000 to initiate the systematic collection of lifestyle
and health information on children of atomic-bomb survivors. The intent
of this program is to determine whether atomic-bomb radiation received
by the parents led to damage in the germ cells that form offspring that
manifested itself as long-term health effects, i.e., whether multifactorial
diseases are increased in the children of atomic-bomb survivors. This study
is a companion to the biochemical genetics program (see below), which looks
directly at mutations in children that may have resulted from parental
The survey includes not only children of atomic-bomb survivors but also,
for the purpose of comparison, children born around the same time whose
parents are not bomb survivors. First, questionnaires were sent by mail
to elicit information on present and past health status, personal habits
such as smoking, drinking, diet, exercise, and the like, and respondents
were also asked about their willingness to participate in the clinical
health examination program. The questionnaires were sent to approximately
24,600 individuals over a period of four years starting in 2000, and about
12,000 people underwent clinical health examinations between 2002 and 2006.
Analysis was conducted, based on data from the mail survey questionnaires
and the clinical health examinations, regarding whether risk of adult-onset
multifactorial diseases such as hypertension, diabetes mellitus, etc. increases
in relation to parental radiation exposure.
As a result, no evidence for increased prevalence of such diseases was observed.
This study was reviewed by independent scientific and ethical review committees
consisting of non-RERF scientists and experts in ethics and law.
The 4-year-cycle incidence study through health examinations started in November 2010, and has been underway.
The focus of this program is on elucidating whether atomic-bomb
radiation exposure led to mutations in germ cells (sperm and ova)
that resulted in abnormalities in children of the survivors (i.e.,
possible genetic effects due to parental radiation exposure). Studies
on DNA from family members of the A-bomb survivors are being carried
out to search for differences in germ-cell mutation rates between
exposed and unexposed parents. To determine whether variations in
DNA in the children are inherited (i.e., already present in the
parents prior to their A-bomb radiation exposure) or are the results
of germ-cell mutations (possibly due to radiation exposure), nucleotide
sequences of DNA from father-mother-child trios are compared. A
variant of DNA in a child that is not observed in either biological
parent is considered to be a de novo (new) germ-cell mutation.
The occurrence of such mutations, if they are found to exist, would
then be compared to the parents' radiation dose to see if radiation
is a possible explanatory factor. The current projects are:
- Establishment of samples for future molecular studies
With the recent rapid progress in molecular biology, it has become possible
to study genes (DNA) and their products (RNA and proteins) directly. Permanent
cell lines have been established from peripheral B lymphocytes from parents
and all available children of 500 families in which at least one parent
was exposed to A-bomb radiation and 500 control families in which parents
were either exposed to a gonadal dose of less than 0.01 Gy or not exposed.
Cells collected from these families are cryopreserved in liquid nitrogen
- Two-dimensional DNA electrophoresis
With this method, DNA samples are fragmented with restriction
enzymes, and the cleaved parts are labeled with radioisotopes.
Then, the samples are separated by the two-dimensional electrophoresis.
Autoradiography of dried electrophoresed gels is performed in
order to visualize DNA fragment spots on X-ray films to produce
images. On one image, 2,000-3,000 DNA fragments are observed
as spots. By comparative analysis of images of father/mother/child
using a computer program, germline mutations of many genes are
- Microarray-based comparative genomic hybridization (array
Comparative genomic hybridization (CGH) on a DNA-microarray
(array CGH) can measure the differences in copy number of genes
between samples, which occur as a result of chromosome deletions,
duplications, and amplifications. This method has also abilities
for large scale screening of the genetic alterations in a fully
automated fashion. Moreover, this method can scan entire human
genome on a few slide glasses. So, it appears that this method
can provide voluminous information from a single participant
in our genetic study, and can examine a large number of study
subjects effectively. The array CGH method is one of the best
tools for our genetic studies at DNA level.