(2) in the irradiated groups, the P0 rate was significantly higher (1.8-fold) and the F1 rate was nonsignificantly (1.5-fold) higher compared to controls; and (3) plotted against the parental year of birth (1950–1960, 1961–1965, and 1966–1974), the mutation rate in the exposed F1 generation showed a negative correlation (i.e., decreased) with the parental year at birth, with the highest rate in the 1950–1960 cohort (similar to that in the P0 families) and much lower in the later two time periods (similar to that in the control cohorts).

The authors have interpreted these findings as follows: (1) all P0 parents born between 1926 and 1948 would have been directly exposed to relatively high levels of radiation from the nuclear tests, and this would explain the 1.8-fold increase in mutation rate; (2) F1 parents born between 1950 and 1956 would be heterogeneous with respect to the doses received: some would also have been exposed to high radiation doses, while those born later would have received considerably lower doses, and this heterogeneity in the parental doses could explain the 1.5-fold increase in mutation rate; and (3) the negative correlation with the year of birth may reflect the decreased exposure after the decay of radioisotopes in the late 1950s and after the cessation of surface and atmospheric nuclear tests.

Other Population Studies

In the mid-1990s, subsequent to publication of the radiation studies with mouse ESTR loci discussed earlier, Kodaira and colleagues (1995) conducted a pilot feasibility study on germline instability in cell lines established from the children of atomic bomb survivors in Japan. The cell lines were from 64 children from the 50 most heavily exposed families (combined gonadal equivalent dose of 1.9 Sv) and 50 children from control families. Mutations at six minisatellite loci were studied using the following six probes: Pc-1, 8TM-18, ChdTC15, p8g3, 8MS1, and CEB1. A total of 28 mutations were found, but these were at the p8g-3, 8MS-1, and CEB-1 loci only, and there were no mutations at the other three loci. Twenty-two of these were in the controls (of 1098 alleles tested; 2%), and six were in children from irradiated parents (among 390 alleles; 1.5%). Thus, there was no significant difference in mutation frequencies between the control and the exposed groups. The use of probes 33.16 and 33.15 in subsequent work did not alter the above conclusion (Satoh and Kodaira 1996; Satoh and others 1996).

The discrepancy between the results of Kodaira and colleagues, on the one hand, and those of Dubrova and colleagues (1996, 1998b, 2000a, 2000b) in the Belarus and other cohorts discussed earlier appears real. To what extent this might be due to differences in type and duration of radiation exposure remains unclear. For instance, the A-bomb survivors were externally exposed to considerable acute doses of radiation, whereas in the Belarus, Ukraine, and Semipalatinsk studies the exposures were chronic (both internal and external). Secondly, in the case of A-bomb survivors, most of their children were born more than 10 years after the single, acute parental exposure; in Belarus and Ukraine, however, the affected areas have been irradiated constantly since the Chernobyl accident. Finally, the Japanese data are derived from families in which most of the children were born to parents of whom only one had sustained radiation; in the work of Dubrova and colleagues, the data pertain to children for whom both parents had been exposed to chronic irradiation.

Livshits and colleagues (2001) found that the children of Chernobyl cleanup workers (liquidators) did not show an elevated rate of minisatellite mutations compared to a Ukrainian control group. The dose estimate for the liquidators was <0.25 Gy but is subject to uncertainty (Pitkevich and others 1997), and the main exposure was from external γ-irradiation (with a relatively minor contribution from the intake of radionuclides) received as repeated small daily doses. Interestingly, children conceived within 2 months of the fathers’ employment had a higher mutation rate than those conceived more than 4 months after the fathers stopped working there. This would be consistent with an effect on cells undergoing spermatogenesis, but not on spermatogonial stem cells. However, none of these differences was statistically significant.

More recently, Kiuru and colleagues (2003) compared the frequencies of minisatellite mutations among children of 147 Estonian Chernobyl cleanup workers. The comparisons were within families (i.e., between children born before and after their fathers were exposed to radiation). The post-Chernobyl children (n = 155) were conceived within 33 months of their fathers’ return from Chernobyl; the “control” children were siblings (n = 148) born prior to the accident. Mutations were studied at eight minisatellite loci (CEB1, CEB15, CEB25, CEB36, MS1, MS31, MS32, and B6.7). The estimated mean dose to the workers was 100 ± 60 mSv, with fewer than 1.4% of the cohort receiving more than 250 mSv.

A total of 94 mutations (42 in the pre-Chernobyl group and 52 in the post-Chernobyl group) were found at the eight tested loci. Within-family (i.e., pre- and post-Chernobyl) comparisons of mutation rates showed that the post-Chernobyl children had a slightly but not significantly higher mutation rate (0.042 per band) than the pre-Chernobyl children (0.035 per band) with an odds ratio of 1.33 (95% CI: 0.80, 2.20). The available data do not permit an assessment of the extent to which differences in paternal age might have contributed to this difference. When the cleanup workers were subdivided according to their radiation doses, the mutation rate in children born to fathers with recorded doses of 200 mSv, showed a nonsignificant increase relative to their siblings; at lower doses there was no difference.

Weinberg and colleagues (2001) screened children born in families of cleanup workers (currently either in Ukraine or Israel) for new DNA fragments (‘mutations’) using “multisite DNA fingerprinting.” In contrast to the results of Livshits and colleagues (2001), they reported a sevenfold



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