Effect of occupational radiation exposures on chromosome aberration rates in former plutonium workers.

A fluorescence in situ hybridization (FISH) method was used to measure chromosome aberration rates in lymphocytes of 30 retired plutonium workers with combined internal and external radiation doses greater than 0.5 Sv along with 17 additional workers with predominantly external doses below 0.1 Sv. The former group was defined as high-dose and the latter as low-dose with respect to occupational radiation exposure. The two groups were compared to each other and also to 21 control subjects having no history of occupational radiation exposure. Radiation exposures to the high-dose group were primarily the result of internal depositions of plutonium and its radioactive decay products resulting from various work-related activities and accidents. The median external dose for the high-dose group was 280 mSv (range 10-730) compared to a median of 22 mSv (range 10-76) for the low-dose group. The median internal dose to the bone marrow for the high-dose group was 168 mSv (range 29-20,904) while that of the low-dose group was considered negligible. Over 200,000 metaphase cells were analyzed for chromosome aberrations by painting pairs 1, 4 and 12 in combination with a pancentromeric probe. Additionally, 136,000 binucleated lymphocytes were analyzed for micronuclei in parallel cultures to assess mitotic abnormalities arising from damaged chromosomes. The results showed that the frequency of structural aberrations affecting any of the painted chromosomes in the high-dose group correlated with the bone marrow dose but not with the external dose. In contrast, the frequency of micronuclei did not vary significantly between the study groups. The total translocation frequency per genome equivalent x 10(-3) +/- SE was 4.0 +/- 0.6, 9.0 +/- 1.1 and 17.0 +/- 2.1 for the control, low-dose and high-dose groups, respectively. Statistical analysis of the data showed that the frequency of total translocations and S-cells correlated with the bone marrow dose, with P values of 0.005 and 0.004, respectively. In contrast, these two end points did not correlate with the external dose, with P values of 0.45 and 0.39, respectively. In conclusion, elevated rates of stable chromosome aberrations were found in lymphocytes of former workers decades after plutonium intakes, providing evidence that chronic irradiation of hematopoietic precursor cells in the bone marrow induces cytogenetically altered cells that persist in peripheral blood.