Presentation 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

勝部, 孝則  ,  Qiang, LIU  ,  DU Liqing  ,  Yan, WANG  ,  Chang, XU  ,  二宮, 康晴  ,  王, 冰

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.

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