Misrepair of DNA double-strand breaks after exposure to heavy-ion beams causes a peak in the LET–RBE relationship with respect to cell killing in DT40 cells
| Autor: | Yoshiya Furusawa, Mizuho Aoki-Nakano |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
DNA Repair
DNA repair Health Toxicology and Mutagenesis Linear energy transfer Apoptosis Biology Radiation Dosage misrepair chemistry.chemical_compound relative biological effectiveness Cell Line Tumor Relative biological effectiveness Animals Sister chromatids DNA Breaks Double-Stranded Heavy Ions Radiology Nuclear Medicine and imaging Chromosome Aberrations Genetics Ku70 Radiation linear energy transfer fungi Dose-Response Relationship Radiation Neoplasms Experimental sensitivity Molecular biology heavy ion Cell killing chemistry Homologous recombination Chickens DNA |
| Zdroj: | Journal of Radiation Research |
| ISSN: | 1349-9157 0449-3060 |
| DOI: | 10.1093/jrr/rrt064 |
| Popis: | To determine the radiobiological mechanisms underlying relative biological effectiveness (RBE) and the repair efficiencies of DNA double-strand breaks (DSBs) as a function of linear energy transfer (LET), we exposed cells of the chicken B-lymphocyte cell line DT40 and its DSB repair pathway-deficient derivatives to heavy-ion beams produced at the Heavy-Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS), Chiba, Japan. The relationship between LET and cell lethality was investigated in the DNA DSB repair gene knockouts Ku70(-/-), Rad54(-/-), and Ku70(-/-)Rad54(-/-), and in the wild-type cells. We found that cell-cycle stage and activity of the DNA DSB repair pathways influence LET-mediated biological effects. An expected LET-RBE relationship was observed in the cells capable of DNA repair, but no peak was found in the RBE with respect to cell survival in the Ku70(-/-)Rad54(-/-) cells or in Ku70(-/-) cells in the G1 and early S cell-cycle phases (when no sister chromatids were present and homologous recombination could not occur). These findings suggest that the peak in RBE is caused by deficient repair of the DNA DSBs. |
| Databáze: | OpenAIRE |
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