| Autor: |
Oskamp, Dominik, Jaeger, Alexandra, Pomplun, Ekkehard, Kriehuber, Ralf |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Zdroj: |
14. Jahrestagung der Gesellschaft für Biologische Strahlenforschung, GBS, Rheinbach, Germany, 2011-09-13-2011-09-16 |
| Popis: |
Introduction: Theoretical calculations and experimental findings suggest that DNA-incorporated Auger electron emitter (AEE) cause primarily complex DNA lesions. Recent cell cycle analysis revealed, that 5-(125)iodine-2'-deoxyuridine (I-125-UdR)-exposed SCL-II cells display a pronounced and rather long-lasting G2/M cell cycle arrest. We studied therefore in more detail whether the observed G2/M arrest is of permanent or temporary nature and thereby examined the average number of decay per cell necessary to induce a long-lasting cell cycle arrest in SCL-II cells.Methods: SCL-II cells were synchronized in G1-phase and incubated with 0.1, 1, 4 and 8 kBq/ml of I-125-UdR during S-phase so that approximately 90 % of the cells were subsequently labeled. Cell cycle analysis was performed by flow cytometry (Click-iT EdU cell proliferation assay and Sytox Green nucleic acid stain) up to 4 d post-labeling with a constant sampling every 8 h post-labeling.Results: DNA-incorporated I-125-UdR decelerated SCL-II cell cycle progression. Cell cycle perturbances were observed and a pronounced and prolonged G2/M-phase arrest was detected at activity concentration of 4 kBq/ml I-125-UdR. Up to 70 % of the cells were arrested in G2/M-phase up to 38 h post-labeling with 8 kBq/ml I-125-UdR. Moreover, a distinct population of G2/M-arrested cells was detectable up to 94 h post-labeling. As shown by parallel EdU staining these cells were permanently caught in the first G2/M cell cycle phase post-labeling. On average one decay every 90 s per DNA/cell was calculated to induce a permanent G2/M arrest in SCL-II cells.Conclusions: Incorporated I-125-UdR induces major cell cycle perturbances in SCL-II cells. The observed permanent G2/M arrest suggests a threshold in terms of decays per time per cell and hence persisting DNA damage beyond no G2/M release seems to occur. This implies different levels of DNA damage for the induction and the release of the G2/M arrest in SCL-II cells. Funded by Bundesministerium für Umwelt, Natur und Reaktorsicherheit (BMU), Bundesamt für Strahlenschutz; Project No.: 3608S03002 |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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