mFISH Analysis Reveals Complexity of Chromosome Aberrations in Individuals Occupationally Exposed to Internal Plutonium: A Pilot Study to Assess the Relevance of Complex Aberrations as Biomarkers of Exposure to High-LET α Particles

Anderson, R. M., Tsepenko, V. V., Gasteva, G. N., Molokanov, A. A., Sevan'kaev, A. V. and Goodhead, D. T. mFISH Analysis Reveals Complexity of Chromosome Aberrations in Individuals Occupationally Exposed to Internal Plutonium: A Pilot Study to Assess the Relevance of Complex Aberrations as Biomarkers of Exposure to High-LET α Particles. Radiat. Res. 163, 26–35 (2005). We recently demonstrated that a significant proportion of apparently stable insertions induced after exposure to a mean of one α particle/cell, detected using three-color FISH, were part of larger unstable complexes when visualized by 24-color FISH. Interestingly, regardless of the long-term persistence capability of the cell, the complexity of each α-particle-induced complex appeared to be specific to the nuclear traversal of a single α particle. To assess whether aberrations of a similar complexity are observed in vivo and also to examine the usefulness of detecting such aberrations as a biomarker of chronic exposure to α particles, we have carried out a limited pilot study of Russian workers with large body burdens of α-particle-emitting plutonium. We found unstable cells containing non-transmissible complex aberrations in all of the plutonium-exposed subjects analyzed by mFISH. In addition, all of the complexes seen were consistent with those previously observed in vitro. Non-transmissible complex aberrations were more common than transmissible-type complexes, consistent with ongoing/chronic exposure, and insertions were dominant features of both types of complex. Accordingly, this preliminary study supports the proposal that aberration complexity and non-transmissibility are the major cytogenetic features of α-particle exposure that could potentially be exploited as a specific indicator of chronic exposures to high-LET α particles.