Chromosome aberrations induced by the Auger electron emitter 125I

Abstract

DNA-associated Auger electron emitters (AEE) cause cellular damage leading to high-LET type cell survival curves indicating an enhanced relative biological effectiveness. Double strand breaks (DSBs) induced by Iodine-125-deoxyuridine (125I-UdR) decays are claimed to be very complex. To elucidate the assumed genotoxic potential of 125I-UdR, chromatid aberrations were analysed in exposed human peripheral blood lymphocytes (PBL).PBL were stimulated with medium containing phytohaemagglutinin (PHA). After 24h, cultures were labelled with 125I-UdR for 18h (activity concentration 1–45 kBq) during the S-phase. Following standard cytogenetic procedure, at least 100 metaphases were analysed microscopically for each activity concentration. Cell death was measured by apoptosis assay using flow cytometry. Radiation doses were determined by using point kernel calculations.After 18h labelling with 125I-UdR the cell cycle distribution is severely disturbed. About 40% of PBL are fully labelled and 20% show a moderate labelling of 125I-UdR, whereas 40% of cells remain un-labelled. The dose-response relationship fits to a polynomial curve in the low dose range, whereas a linear fit supplies a better estimation in the high dose range. Even the lowest dose of 0.2Gy leads to a 13-fold increase of aberrations compared to the controls. On average every fifth 125I-decay produces a single chromatid aberration 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 0.2Gy. Efficiently labelled cells displaying a prolonged cell cycle compared to moderately labelled cells and cell death contribute substantially to the desynchronisation of the cell cycle. Our data, showing for the first time, that one 125I-decay induces ∼ 0.2 chromatid aberrations, are in very good accordance to DSB data, stating that ∼0.26 DSB are induced per decay, indicating that approximately every DSB is converted into a chromatid aberration.