title: 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.
abstract: 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.
authors.affiliation: MRC Radiation and Genome Stability Unit, Harwell, Didcot, Oxfordshire, OX11 0RD, United Kingdom. r.anderson@har.mrc.ac.uk
authors.forename: Rhona M
authors.initials: RM
authors.lastname: Anderson
authors.forename: Viktoria V
authors.initials: VV
authors.lastname: Tsepenko
authors.forename: Galina N
authors.initials: GN
authors.lastname: Gasteva
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Molokanov
authors.forename: Aleksander V
authors.initials: AV
authors.lastname: Sevan'kaev
authors.forename: Dudley T
authors.initials: DT
authors.lastname: Goodhead
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001822:Body Burden; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000528:radiation effects*; D004252:DNA Mutational Analysis / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D009688:Nuclear Reactors; D016273:Occupational Exposure / Q000032:analysis*; D010865:Pilot Projects; D011829:Radiation Dosage; D011835:Radiation Protection / Q000379:methods; D011874:Radiometry / Q000379:methods*; D012062:Relative Biological Effectiveness; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers