| From 1949 through 1989 nuclear weapons testing was carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS), which resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk, and Pavlodar regions of Kazakhstan. In order to determine whether the whole-body radiation received by the residents as a consequence of the test explosions resulted in detectable biological responses, 233 blood samples (139 cases and 94 control) and accompanying background information were obtained and shipped to the United States for evaluation. This dissertation reports the results of the analysis of the demographic data and biodosimetry using the glycophorin A (GPA) locus in vivo somatic cell mutation assay applied to the 233 blood samples. The linear regression of the Ø/N and N/N GPA VFs showed mixed results. In the GPA Ø/N VFs there was no positive association with age (P = 0.94), smoking status (P = 0.76), or reported dose of exposure (P = 0.14) with in the total study cohort. Within the individual generational groups no significant level of association was found in any of the generations for age, smoking status or estimated total dose of exposure [Po: Age (P = 0.16), Smoking (P = 0.34), and Exposure Dose (P = 0.21); F1; Age (P = 0.63), Smoking ( P = 0.98), and Exposure Dose (P = 0.63); and F 2: Age (P = 0.40), Smoking (P = 0.99), and Exposure Dose (P = 0.40)]. As for the GPA N/N VFs a significant level of association was found with estimated total dose of exposure (P = 0.01) within the entire study cohort. Thus homozygous VFs seemed to be a better indicator of this cohort's past radiation exposure than the hemizygous VFs. This is contrary to what has been reported in previous studies where gene deletion, which would produce hemizygous variant cells, is a major mechanism for radiation-induced mutation as opposed to mitotic recombinational effects that leads to homozygous variant cells. These data suggest that the average radiation exposure to the Po residents approximated 25 cGy. For the F1 and F2 residents the results indicate that the average radiation exposure did not exceed 10 cGy, the minimum levels at which radiation effects might be detectable by the assay. The results of a linear regression model that included the potential confounding effects of age and smoking status, found age to have a significant positive effect on GPA N/N variant frequencies (VFs). Although the protracted nature of the exposure may have reduced the efficiency of induction of GPA locus mutations, it is likely that the actual physical doses received by the exposed population were too low to result in radiation damage to erythroid stem cells, which can be detected reliably by this biodosimetry method. |
