Cytogenetic fingerprints of past exposure to high LET radiations
Long-lived, sensitive, and specific biomarkers of particular mutagenic agents are much sought after, and potentially have broad applications in the field of cancer biology, epidemiology, and prevention. Many clastogens induce a spectrum of chromosome aberrations and some of them can be exploited as biomarkers of exposure. Densely-ionising radiations, such as alpha particles (from radon or plutonium) or neutrons, preferentially induce intra-chromosomal aberrations and complex chromosome aberrations, which can be detected by the 24 colour multifluor fluorescence in situ hybridization (mFISH) and by multicolour banding (mBAND) technique. We report the detection and quantification of stable complex chromosome aberrations in lymphocytes of healthy former nuclear-weapons workers, who were exposed many years ago to plutonium or gamma rays, or both, at the Mayak weapons complex in Russia. We have analyzed peripheral blood lymphocytes from these individuals for the presence of persistent complex chromosome aberrations and of intra-chromosomal aberrations such as peri-, para-centric inversions and deletions. Even many years after occupational exposure, more than half the blood cells of the healthy plutonium workers contain large (> 6 Mbp) intra-chromosomal rearrangements. The yield of these intra-chromosomal aberrations was highly correlated with plutonium dose to the bone marrow. Significantly elevated yields of complex chromosome translocations were detected in the highly-exposed plutonium workers, but not in the group who were exposed only to high doses of gamma radiation. No such differences were found for simple chromosomal aberrations. The results suggest that stable complex chromosomal translocations and intra-chromosomal alterations represent a long-lived, quantitative, low-background biomarker of densely-ionising radiation, for human populations exposed many years ago.