Chromosome aberrations induced by the Auger electron emitter 125I

Schmitz, Sabine; Oskamp, Dominik; Kriehuber, Ralf; Pomplun, Ekkehard

doi:10.1016/j.mrgentox.2015.08.007

Journal Article

FZJ-2015-06470

Chromosome aberrations induced by the Auger electron emitter 125I

Schmitz, S. (Corresponding author)FZJ* ; Oskamp, D.FZJ* ; Pomplun, E. ; Kriehuber, R.FZJ*

2015
Elsevier Science Amsterdam [u.a.]

Mutation research / Genetic toxicology and environmental mutagenesis 793, 64 - 70 (2015) [10.1016/j.mrgentox.2015.08.007] special issue: "Insights into formation and consequences of chromosome aberrations: Report on the 11th International Symposium on Chromosomal Aberrations (ISCA 11)"

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Please use a persistent id in citations: http://hdl.handle.net/2128/15333 doi:10.1016/j.mrgentox.2015.08.007

Abstract: DNA-associated Auger electron emitters (AEE) cause cellular damage leading to high-LET type cell survivalcurves indicating an enhanced relative biological effectiveness. Double strand breaks (DSBs) induced byIodine-125-deoxyuridine (125I-UdR) decays are claimed to be very complex. To elucidate the assumedgenotoxic potential of125I-UdR, chromatid aberrations were analysed in exposed human peripheral bloodlymphocytes (PBL).PBL were stimulated with medium containing phytohaemagglutinin (PHA). After 24 h, cultures werelabelled with125I-UdR for 18 h (activity concentration 1–45 kBq) during the S-phase. Following stan-dard cytogenetic procedure, at least 100 metaphases were analysed microscopically for each activityconcentration. Cell death was measured by apoptosis assay using flow cytometry. Radiation doses weredetermined by using point kernel calculations.After 18 h labelling with125I-UdR the cell cycle distribution is severely disturbed. About 40% of PBL arefully labelled and 20% show a moderate labelling of125I-UdR, whereas 40% of cells remain un-labelled. Thedose-response relationship fits to a polynomial curve in the low dose range, whereas a linear fit suppliesa better estimation in the high dose range. Even the lowest dose of 0.2 Gy leads to a 13-fold increaseof aberrations compared to the controls. On average every fifth125I-decay produces a single chromatidaberration in PBL. Additionally, a dose-dependent increase of cell death is observed.125I-UdR has a very strong genotoxic capacity in human PBL, even at 0.2 Gy. Efficiently labelled cellsdisplaying a prolonged cell cycle compared to moderately labelled cells and cell death contribute substan-tially to the desynchronisation of the cell cycle. Our data, showing for the first time, that one125I-decayinduces ∼ 0.2 chromatid aberrations, are in very good accordance to DSB data, stating that ∼0.26 DSB areinduced per decay, indicating that approximately every DSB is converted into a chromatid aberration.

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