量研学術機関リポジトリ「QST-Repository」は、国立研究開発法人 量子科学技術研究開発機構に所属する職員等が生み出した学術成果（学会誌発表論文、学会発表、研究開発報告書、特許等）を集積しインターネット上で広く公開するサービスです。 Welcome to QST-Repository where we accumulates and discloses the academic research results(Journal Publications, Conference presentation, Research and Development Report, Patent, etc.) of the members of National Institutes for Quantum and Radiological Science and Technology.
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Artemis and XRCC4 are members of core factors for non-homologous end joining (NHEJ), a primary repair pathway of DNA double-strand breaks (DSBs). To clarify the participation of Artemis and XRCC4 in DNA damage response (DDR) to high-LET ionizing irradiation (IR), we examined the cellular responses of isogenic human cell lines deficient for these factors (Artemis-/- and XRCC4-/- cells) and a parental HCT116 cells to carbon ion-beams. Substantial increase in sensitivity of Artemis-/- and XRCC4-/- cells to carbon ion-beams as compared to HCT116 cells demonstrated participation of Artemis and XRCC4 in DDR to high-LET IR. Remarkably, the values for relative biological effectiveness (RBE) of carbon ion-beams to X-rays on killing of the Artemis-/-, XRCC4-/- and HCT116 cells appeared to be 2.7, 2.8 and 3.0, respectively. This result is inconsistent with previous reports showing that high-LET IR is much effective as compared to low-LET IR on killing of most cell lines, but not on killing of NHEJ-deficient cells including Ku70, Ku80 and DNA-PKcs mutant lines. To address this discrepancy, we have started to examine induction and repair of DSBs in the Artemis-/-, XRCC4-/- and HCT116 cells following irradiation of carbon ion-beams by gamma-H2AX nuclear foci analyses.
重粒子線に対する細胞応答におけるDNA損傷応答関連因子の機能に関する研究
