Chromosome Aberrations induced by the Auger electron emitter I-125
Chromosome Aberrations induced by the Auger electron emitter I-125
Introduction: DNA-associated Auger-electron emitters (AEE) cause cellular damage leading to high-LET type cell survival curves indicating an enhanced relative biological effectiveness. DNA double strand breaks (DSBs) induced by Iodine-125-deoxyuridine (I-125-UdR) decays are claimed to be very comple...
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Personal Name(s): | Schmitz, Sabine (Corresponding author) |
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Oskamp, Dominik / Pomplun, Ekkehard / Kriehuber, Ralf | |
Contributing Institute: |
Sicherheit und Strahlenschutz, Umgebungsüberwachung,Strahlenbiologie; S-US |
Imprint: |
2015
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Conference: | 8th International Symposium on Physical, Molecular, Cellular and Medical Aspects of Auger Process, Kyoto (Japan), 2015-05-20 - 2015-05-22 |
Document Type: |
Poster |
Research Program: |
Addenda |
Subject (ZB): | |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Introduction: DNA-associated Auger-electron emitters (AEE) cause cellular damage leading to high-LET type cell survival curves indicating an enhanced relative biological effectiveness. DNA double strand breaks (DSBs) induced by Iodine-125-deoxyuridine (I-125-UdR) decays are claimed to be very complex. To elucidate the assumed genotoxic potential of DNA-associated AEE, chromosome 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 labelled with I-125-UdR for 18 h (activity concentration 1 – 45 kBq) during the S-phase. Following standard cytogenetic procedure, at least 100 metaphases were analyzed microscopically for each activity concentration. Cell death was measured by apoptosis assay using flow cytometry. Radiation doses were determined by using point kernel calculations.Results: After 18 h labeling with I-125-UdR the cell cycle distribution is severely disturbed. About 40 % of PBL are fully labeled and 20 % show a moderate labeling of I-125-UdR, whereas 40 % of cells remain unlabeled. I-125-UdR primarily induces chromatid-type aberrations. The dose-response relationship fits well 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 0.2 Gy leads to significant damage and to a 13-fold increase of aberrations compared to the controls. On average every fifth I-125-decay produces a single chromatid aberration in PBL. In addition, 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 cellular doses of about 0.2 Gy. Efficiently labeled cells displaying a prolonged cell cycle compared to moderately labeled cells and cell death contribute substantially to the desynchronisation of the cell cycle. Our data, showing that one I-125-decay induces 0.2 chromatid aberrations, are in very good accordance to the data of Sedelnikova [1] and Yasui [2] who found 0.26 DSB per decay, indicating that approximately every DSB is converted into a chromatid aberration.[1] O.A. Sedelnikova et al. Radiation Research 158, 486 (2002)[2] L.S. Yasui, Int. J. Radiat. Biol., 80, 895 (2004) |