% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @INPROCEEDINGS{Schmitz:188031, author = {Schmitz, Sabine and Oskamp, Dominik and Pomplun, Ekkehard and Kriehuber, Ralf}, title = {{C}hromosome aberrations induced by the {A}uger emitter {I}-125}, reportid = {FZJ-2015-01516}, year = {2014}, abstract = {Introduction: 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.}, month = {Sep}, date = {2014-09-12}, organization = {11th International Symposium on Chromosomal Aberrations, Rhodes (Greek), 12 Sep 2014 - 14 Sep 2014}, subtyp = {Invited}, cin = {S-US}, cid = {I:(DE-Juel1)S-US-20090406}, pnm = {899 - ohne Topic (POF3-899)}, pid = {G:(DE-HGF)POF3-899}, typ = {PUB:(DE-HGF)6}, url = {https://juser.fz-juelich.de/record/188031}, }