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000188030 1001_ $$0P:(DE-Juel1)133346$$aSchmitz, Sabine$$b0
000188030 1112_ $$a41st Annual Meeting of the European Radiation Research Society$$cRhodes$$d2014-09-14 - 2014-09-19$$gERR$$wGreek
000188030 245__ $$aChromosome Aberrations induced by the Auger emitter I-125
000188030 260__ $$c2014
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000188030 520__ $$aIntroduction: DNA-associated Auger-electron emitters (AEE) induce cellular damage leading to high-LET type cell survival curves and possess enhanced relative biological effectiveness. DNA dsb induced by Iodine-125-deoxyuridine (I-125-UdR) decays are claimed to be very complex, thus efficiently leading to cell transformation, gene mutation and induction of chromatid aberrations. To elucidate the assumed genotoxic potential of DNA-associated AEE, chromosomal/chromatid aberrations were analyzed in I-125-UdR-exposed human peripheral blood lymphocytes (PBL).Methods: PBL were isolated from whole blood and stimulated with chromosome medium containing phytohaemagglutinin (PHA). After 24 h cultures were labeled with I-125-UdR for 18 h (0.25-4.5 kBq/ml) during the S-phase of the cell cycle. After removal of radioactive medium and washing steps, cells were re-cultured in stimulation medium for further 24 h. Colcemid was added 5.5 h before harvest of cells followed by fixation for aberrations at 71.5 h post-stimulation. All slides were stained with 10 % Giemsa, and 100 metaphases were analyzed microscopically for each dose point.Results: After 18 h labeling with I-125-UdR the cell cycle distribution is severely disturbed. Furthermore, 40% of PBL are fully labelled and 20% show a moderate uptake of I-125-UdR. I-125-UdR primarily induces chromatid-type aberrations. PBL reveal a very broad dose-dependent response spectrum: equal numbers of cells have either no aberration, or display a moderate aberration level (1-9 aberrations). Few cells exhibit a high aberration score (> 10 aberrations). A dose-dependent increase of aberrations is measured in the range of 0.2 to 2 Gy, followed by a plateau between 2 and 4.5 Gy. The data indicate that even the lowest dose of 0.2 Gy leads to significant damage in PBL and to a 4.5-fold increase of aberrations compared to the controls. Furthermore, a dose-dependent increase of cell death is observed.Conclusions: I-125-UdR has a very strong genotoxic capacity in human PBL even at very low doses of about 0.2 Gy. Efficiently labeled cells displaying a prolonged cell cycle compared to moderate labeled cells, and cell death contribute substantially to the desynchronisation of the cell cycle. In summary, it can be concluded that every fourth intracellular I-125 decay give rise to a single chromosome aberration.
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000188030 7001_ $$0P:(DE-Juel1)133339$$aOskamp, Dominik$$b1
000188030 7001_ $$0P:(DE-Juel1)133341$$aPomplun, Ekkehard$$b2
000188030 7001_ $$0P:(DE-Juel1)133469$$aKriehuber, Ralf$$b3$$eCorresponding author
000188030 773__ $$y2014
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