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 alpha particles

• Published in: Radiation research Vol. 163; no. 1; p. 26
• Main Authors: Anderson, Rhona M, Tsepenko, Viktoria V, Gasteva, Galina N, Molokanov, Alexander A, Sevan'kaev, Aleksander V, Goodhead, Dudley T
• Format: Journal Article
• Language: English
• Published: United States 01.01.2005
• Subjects: Biomarkers - analysis; Body Burden; Chromosome Aberrations; Chromosomes - radiation effects; DNA Mutational Analysis - methods; Humans; In Situ Hybridization, Fluorescence - methods; Lymphocytes - radiation effects; Male; Middle Aged; Nuclear Reactors; Occupational Exposure - analysis; Pilot Projects; Radiation Dosage; Radiation Protection - methods; Radiometry - methods; Relative Biological Effectiveness; Reproducibility of Results; Risk Assessment - methods; Risk Factors; Sensitivity and Specificity
• ISSN: 0033-7587; 1938-5404
• DOI: 10.1667/RR3286

We recently demonstrated that a significant proportion of apparently stable insertions induced after exposure to a mean of one alpha 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 alpha-particle-induced complex appeared to be specific to the nuclear traversal of a single alpha 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 alpha particles, we have carried out a limited pilot study of Russian workers with large body burdens of alpha-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 alpha-particle exposure that could potentially be exploited as a specific indicator of chronic exposures to high-LET alpha particles.