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 exposure.
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.

Biochemical genetics

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:

1. 1. 1.Establishment of samples for future molecular studies
      1. 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 at -200℃.

    

   1. 2.Two-dimensional DNA electrophoresis
      1. 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 searched efficiently.

    

   1. 3.Microarray-based comparative genomic hybridization (array CGH)
      1. 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.