m-FISH analysis reveals complexity of chromosome aberrations in individuals occupationally exposed with internal plutonium: A pilot study to assess the relevance of complex aberrations as biomarkers of exposure to high-LET α particles

Abstract

We recently demonstrated that a significant proportion of apparently stable insertions induced after exposure to a mean of 1 α particle/cell, detected using 3-colour FISH, were part of larger unstable complexes when visualised by 24-colour 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 -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 -particle emitting plutonium (Pu). We found unstable cells containing non-transmissible complex aberrations in all of the Pu exposed subjects analysed by m-FISH. 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 on-going/chronic exposure and insertions were dominant features of both type 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