Chromosome translocations are used to estimate the doses of radiation received following occupational or accidental exposure. Biodosimetry relies on the assumption that translocations are not cell-lethal and persist with little or no loss over time. While translocations do exhibit substantially greater persistence than other aberration types (e.g., dicentrics), there is evidence that translocation frequencies also decline over time, at least following acute doses above 1 Gy. To the extent that translocation frequencies decline, the predicted absorbed doses will be underestimated. Yet unknown is whether translocations induced by ionizing radiation at doses below 1 Gy also show significant declines. Here we report on the persistence of translocations induced by 137Cs gamma-rays at acute doses ranging from 0.2 to 4 Gy using peripheral blood lymphocytes from two unrelated healthy male donors. Chromosome aberrations were evaluated by simultaneously painting chromosomes 1, 2, and 4 in red and 3, 5, and 6 in green in cells harvested 2-7 days following exposure and were scored using the PAINT system. Translocations were also enumerated using several other methods and these results are reported separately by us in this issue. For comparison, the persistence of dicentrics, rings, acentric fragments, and color junctions was also evaluated and showed rapid losses with time. The results from both donors provide evidence that translocation frequencies decline with time in a statistically significant manner at doses as low as 0.2-0.3 Gy. The frequency of translocations for all dose groups declined from day 2 to 7 by averages of 39% and 26% for donors 1 and 2, respectively. These data emphasize the importance of considering translocation loss in biological dosimetry long times after exposure.

Chromosome breaks and rearrangements resulting from ionizing radiation can be much more complicated than many investigators thought possible some years ago. The realization that not all translocations are reciprocal, that multiway exchanges occur, and that some double-strand breaks are not repaired prior to mitosis have all contributed to the difficulty of knowing how best to identify, record, evaluate, and report chromosome translocations. Here we describe the results of a series of experiments in which blood from two normal healthy subjects was obtained, irradiated with 137Cs gamma-rays in vitro at doses ranging from 0 (controls) to 4 Gy, and cultured. Cells from each dose group and donor were harvested at days 2, 2.5, 3, 4, 5, and 7 and evaluated for chromosome damage by simultaneously painting chromosomes 1, 2, and 4 in red and 3, 5, and 6 in green. The persistence of dicentrics, fragments, rings, insertions, and PAINT translocations are reported separately by us in this issue. In this article, we focus on translocations, characterizing the various types in detail and comparing and contrasting their persistence across all dose groups for both donors. The results indicate that the persistence of all translocation types was sufficient to be used for retrospective dosimetry, although nonreciprocal translocations exhibited diminished persistence compared to the other types. We also characterize the kinetics of the radiation dose responses of the two donors who exhibited significant differences in the induction as well as the persistence of translocations. Based on the evidence presented here, we hypothesize that these individuals differ in the recognition and repair of radiation-induced damage as well as in cell cycle checkpoint control. Despite these differences, the temporal frequency of translocation losses at both the high and low doses was similar for both subjects.