Persistence of Radiation-Induced Translocations in Human Peripheral Blood Determined by Chromosome Painting

Abstract

We have investigated the persistence of translocations and other types of chromosome damage with time using human peripheral blood acutely exposed in vitro to 137Cs gamma rays at doses ranging from 0.5 to 4 Gy. Freshly drawn blood from one donor was irradiated and metaphase chromosomes were prepared 2 to 7 days after exposure. Chromosomes 1, 2 and 4 were painted red-orange and chromosomes 3, 5 and 6 were painted green by fluorescence in situ hybridization (FISH) using "semi-directly" labeled whole-chromosome painting probes. This type of labeling combines direct and indirect labeling and showed significant advantages over both these other methods. All types of structural chromosome aberrations were classified by the Protocol for Aberration Identification and Nomenclature Terminology (PAINT) system. The yields of dicentric chromosomes, acentric fragments and ring chromosomes diminished with time as expected. Translocations exhibited greater persistence but showed a clear and statistically significant reduction in frequency at all doses. The mathematical model suggested that the translocation frequencies would reach a plateau of approximately 4, 15, 51, 106 and 179 translocations per 100 cell equivalents after irradiation with 0.5, 1, 2, 3 and 4 Gy, respectively. When translocations were classified by the conventional system, an analysis of the distribution of translocations and dicentrics per cell indicated that both types of exchanges were Poisson-distributed 48 h postirradiation. However, cells bearing translocations have a higher possibility of having dicentrics than cells without translocations. These findings suggest that dicentrics may contribute to a decline of translocation frequencies with time, and that some translocations are not completely persistent. The results obtained here using human blood exposed in vitro may influence the use of translocations as a retrospective biodosimeter of exposure to ionizing radiation in humans.

Persistence of chromosome aberrations following acute radiation: II, Does it matter how translocations are scored?

“…These intercepts are the asymptotes approached over time by the frequencies of the various types of translocations in these experiments. As expected, the asymptotes increase with dose and retain their dose dependency, confirming our earlier work [Matsumoto et al, 1998] with a portion of the data evaluated here. The results for the two donors are remarkably similar despite the substantial differences in the translocation frequencies at the intermediate time points (Figs.…”

“…As all main effect terms (donor, dose, and day) and all interactions were highly significant, subsequent analyses to determine the influence of time on the frequency of various translocations were conducted separately for each combination of donor and dose. To examine the influence of time on the number of translocations per cell equivalent, we followed our earlier work [Matsumoto et al, 1998] and transformed the data for regression analyses such that ln ðnumber of translocations per 100 cell equivalents scoredÞ…”

International study of factors affecting human chromosome translocations

“…The frequency of stable translocations is thought to increase with age because they are induced throughout life and undergo little negative selection during mitosis [33,39,40]. However, the reason(s) translocation frequencies increase in a curvilinear manner is unknown.…”

Dose dependency of FISH-detected translocations in stable and unstable cells after ¹³⁷Cs γ irradiation of human lymphocytes in vitro

“…In the literature, several dose-effect curves for translocations after exposure to 60 Co-Á or 137 Cs-Á rays from different laboratories are available (Bauchinger et al, 1993;Tucker et al, 1993;Lucas et al, 1995Lucas et al, , 1997Lindholm et al, 1998;Matsumoto et al, 1998;Finnon et al, 1999;Hsieh et al, 1999). A direct comparison of the results is not possible due to several differences in irradiation conditions and scoring criteria.…”