Chromosome aberrations in workers with exposure to α-particle radiation from internal deposits of plutonium: expectations from in vitro studies and comparisons with workers with predominantly external γ-radiation exposure

Abstract

mFISH analysis of chromosome aberration profiles of 47 and 144 h lymphocyte cultures following exposure to 193 mGy α-particle radiation confirmed that the frequency of stable aberrant cells and stable cells carrying translocations remains constant through repeated cell divisions. Age-specific rates and in vitro dose-response curves were used to derive expected translocation yields in nine workers from the Mayak nuclear facility in Russia. Five had external exposure to γ-radiation, two of whom also had exposure to neutrons, and four had external exposure to γ-radiation and internal exposure to α-particle radiation from incorporated plutonium. Doubts over the appropriateness of the dose response used to estimate translocations from the neutron component made interpretation difficult in two of the workers with external exposure, but the other three had translocation yields broadly in line with expectations. Three of the four plutonium workers had translocation yields in line with expectations, thus supporting the application of the recently derived in vitro α-particle dose response for translocations in stable cells. Overall this report demonstrates that with adequate reference in vitro dose-response curves, translocation yield has the potential to be a useful tool in the validation of red bone marrow doses resulting from mixed exposure to external and internal radiation.

Cytogenetic Biomarkers of Radiation Exposure

“…However, insertions are now being resolved as being part of much larger, mostly, unstable complex rearrangements when visualised by M-FISH ( Figure 2), in keeping with those previously described, meaning the potential transmissibility of these insertions is much lower than previously thought [43,57]. This is reflected by the low relative proportion of complex aberrations which are classified as being of the transmissible-type and the low estimated frequency of damaged, but stable cells [76][77][78]. Accordingly, insertions are characteristic features of both stable and unstable complex aberrations induced after exposure to high-LET radiation.…”

“…The biological reason for this long-term survival of such heavily damaged PBLs is unclear. However, similar observations, at varying frequencies, have been reported elsewhere including in plutonium workers [87][88][89][90], thorotrast patients [85,91], veterans of nuclear testing [92], A-bomb survivors [93], astronauts and patients receiving carbon therapy [81]. Interestingly, Hande et al [79] found a significant correlation with estimated plutonium dose to the bone marrow (from ~500mGy) and yield of complex aberrations suggesting quantification could potentially be used for dose reconstruction.…”

Alpha-Particle-Induced Complex Chromosome Exchanges Transmitted through Extra-Thymic Lymphopoiesis In Vitro Show Evidence of Emerging Genomic Instability

“…The remaining non-transmissible complexes are proposed to represent mature T-cells which remain in their 1 st interphase for months or even years after irradiation, until sampled and artificially stimulated to divide in culture. The biological mechanism for this long-term persistence of such heavily damaged PBLs is unclear however similar observations have been reported elsewhere [ 24 , 49 , 50 ]. Thus, complex chromosome exchanges, irrespective of their stability through cell division, are reliable and useful indicators of chronic α-particle exposure.…”

Chromosome Aberrations Determined by FISH in Radiation Workers from the Sellafield Nuclear Facility

“…On completion of the study, individual dosimetry records were re-examined to confirm external doses and determine the extent of any internal alpha-particle dose. Only those with internal alpha-particle doses ,10 mGy were included, this being recognized from previous in vitro (28) and in vivo studies (29) as likely to result in ,0.5 translocations per 1,000 cells. The current study population of 164 comprised 12 control individuals with cumulative external doses ,50 mGy, 63 with doses 50-249 mGy, 65 with doses 250-499 mGy and 24 with doses .500 mGy.…”