A novel type of X-ray-sensitive Chinese hamster cell mutant with radioresistant DNA synthesis and hampered DNA double-strand break repair
| Autor: | Paul H.M. Lohman, Maklgorzata Z Zdzienicka, W. Jongmans, Govert P. van der Schans, Nicolaas G. J. Jaspers, G. W. C. T. Verhaegh, Bruno Morolli |
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| Rok vydání: | 1995 |
| Předmět: |
DNA Replication
DNA Repair Free Radicals Cell Survival DNA repair DNA damage Mitomycin Mutant CHO Cells Toxicology Chinese hamster Bleomycin Cricetinae Radiation Ionizing Genetics Animals Streptonigrin Enzyme Inhibitors Molecular Biology Etoposide biology DNA synthesis X-Rays Chinese hamster ovary cell Genetic Complementation Test DNA replication DNA biology.organism_classification Molecular biology Cell killing Gamma Rays Topoisomerase I Inhibitors DNA Damage Mutagens |
| Zdroj: | Mutation Research/DNA Repair. 337:119-129 |
| ISSN: | 0921-8777 |
| DOI: | 10.1016/0921-8777(95)00017-e |
| Popis: | It has been shown that the Chinese hamster cell mutant V-C8 is sensitive to different DNA damaging agents, such as mitomycin C (MMC), alkylating agents, UV light, and X-rays. We found that V-C8 is also sensitive to the following radiomimetic agents: bleomycin (approximately 2-fold, based on D10 values), H2O2 (approximately 2-fold), streptonigrin (approximately 11-fold), and etoposide (approximately 8-fold). Two independent spontaneous MMC-resistant revertants isolated from V-C8 cells show a level of cell killing by X-rays, EMS, and UV light which is similar to that of wild-type cells, suggesting that the observed pattern of cross-sensitivity of V-C8 cells to a wide spectrum of DNA damaging agents results from a single mutation. V-C8 cells also display radioresistant DNA synthesis following gamma-irradiation which, however, remained almost unchanged in the V-C8 revertants. The measurement of the level and rate of repair of DNA single- and double-strand breaks (SSBs and DSBs, respectively) by the DNA elution technique showed that the V-C8 mutant has a slower repair of DSBs induced by gamma-rays. The described unique phenotype of V-C8 cells suggested that V-C8 represents a novel type of mutant amongst X-ray-sensitive hamster cell mutants. To confirm this, complementation analysis with other X-ray-sensitive mutants was performed. V-C8 cells were fused with EM9, XR-1, xrs5, sxi-1, V-3, V-E5, irs3, and BLM2 mutant cells, representing different complementation groups. All the obtained hybrids regained X-ray resistance (or bleomycin resistance in the case of V-C8/BLM2 hybrids) similar to that of wild-type cells, indicating that V-C8 represents a new complementation group. The results presented indicate that V-C8 is defective in a gene involved in a pathway operating in the responses to different DNA damaging agents in mammalian cells. |
| Databáze: | OpenAIRE |
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