Allalunis-Turner J, Barron G M, Day R S
Experimental Oncology, Cross Cancer Institute and Department of Oncology, University of Alberta, Edmonton, Canada.
Radiat Res. 1997 Mar;147(3):284-7.
Cells respond to radiation-induced DNA damage in a cell cycle phase-specific manner as shown by (1) variation in radiosensitivity across the cell cycle and (2) checkpoints in G1 and G2 phase at which arrest of progression of cells through the phases of the cell cycle occurs. We studied these processes in cells of human glioma cell lines which lack (M059J(PK-)) or express (M059K(PK+)) DNA-dependent protein kinase (DNA-PK) activity. Cell populations enriched with cells of a specific cell cycle phase were y-irradiated and analyzed for cell survival. Although both cell lines were relatively sensitive in G1 phase and resistant in S phase, the differential sensitivity was greater in M059J(PK-) cells. In the studies on checkpoints, unsynchronized cells were irradiated and examined for evidence of cell cycle arrest. Neither cell line showed a postirradiation G1-phase arrest, presumably because of mutant p53 status. For M059J(PK-) cells, all doses tested (2.5-10 Gy) resulted in a significant increase in the proportion of G2/M-phase cells; however, for M059K(PK+) cells, a significant increase in G2/M phase was observed only after 10 Gy. These results suggest that the ability to activate the G2-phase checkpoint remains intact in cells which lack DNA-PK activity.
细胞以细胞周期阶段特异性方式对辐射诱导的DNA损伤作出反应，这表现为：(1) 整个细胞周期放射敏感性的变化；(2) G1期和G2期的检查点，细胞在这些检查点处会停止通过细胞周期各阶段的进程。我们在缺乏（M059J(PK-)）或表达（M059K(PK+)）DNA依赖性蛋白激酶（DNA-PK）活性的人胶质瘤细胞系细胞中研究了这些过程。对富含特定细胞周期阶段细胞的细胞群体进行γ射线照射，并分析细胞存活率。虽然两个细胞系在G1期都相对敏感而在S期都具有抗性，但M059J(PK-)细胞中的差异敏感性更大。在检查点的研究中，对未同步化的细胞进行照射，并检查细胞周期停滞的证据。两个细胞系均未显示照射后G1期停滞，推测是由于p53突变状态所致。对于M059J(PK-)细胞，所有测试剂量（2.5 - 10 Gy）均导致G2/M期细胞比例显著增加；然而，对于M059K(PK+)细胞，仅在10 Gy照射后才观察到G2/M期显著增加。这些结果表明，在缺乏DNA-PK活性的细胞中，激活G2期检查点的能力仍然完好无损。
