Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks
Hypersensitivity of ataxia telangiectasia fibroblasts to ionizing radiation is associated with a repair deficiency of DNA double-strand breaks
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DOI：
10.1080/095530097143266
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发表时间：
1997-09-01
影响因子：
2.6
通讯作者：
Malaise, EP
中科院分区：
文献类型：
--
作者：
Foray, N;Priestley, A;Malaise, EP
我们研究了11个非转化的人成纤维细胞系的内在辐射敏感性，潜在致死性损伤（PLD）的修复和辐射诱导的DNA双链断裂（DSB）的修复率，其中4个是纯合的A-T突变和两个是杂合的（A-TH）。所有实验都是在生长的平台期（97-99%的细胞处于G 0/G1）的细胞上进行的。在4 ℃下给予30戈伊的剂量，A-T细胞系具有高达6小时的更快的修复速率，之后修复曲线与对照的修复曲线相交，使得A-T细胞中24小时的残余损伤更高。在37 ℃低剂量率（1 c戈伊.min（-1））下的辐照在A-T细胞和对照之间产生了更显著的差异：由于A-T细胞中一小部分DSB的修复缺陷，在5-40戈伊剂量下，A-T细胞中的残留DSB水平总是高于对照。两种方案显示A-TH细胞系的DSB修复率介于A-T细胞和对照细胞的DSB修复率之间。37 ℃照射后残留的DSB与固有的放射敏感性以及PLD修复的程度之间存在定量关系。在未转化的对照和A-T细胞系中，在照射之前和之后都有非常少的凋亡细胞。总之，这些结果支持DSB修复缺陷是与A-T突变相关的超敏反应机制的论点。
We have studied the intrinsic radiosensitivity, repair of potentially lethal damage (PLD) and the repair rate of radiation-induced DNA double-strand breaks (DSB) in 11 non-transformed human fibroblast cell lines, four of which were homozygous for the A-T mutation and two that were heterozygous (A-TH). All the experiments were done on cells in plateau phase of growth (97-99% of cells in G0/G1). With a dose of 30 Gy delivered at 4 degrees C, the A-T cell lines had faster repair rates of up to 6 h, after which the repair curve crossed that of the control so that the residual damage at 24 h was higher in the A-T cells. Irradiation at 37 degrees C at low dose rate (1 cGy.min(-1)) produced even more marked differences between the A-T cells and controls: the residual DSB level was always higher in A-T cells than controls at doses of 5-40 Gy, due to defective repair of a small fraction of DSB in A-T cells. The two protocols showed DSB repair rates for the A-TH cell lines that were intermediate between those of the A-T and control cells. There was a quantitative relationship between the residual DSB after irradiation at 37 degrees C and the intrinsic radiosensitivity, and with the extent of PLD repair. There were very few apoptotic cells in the non-transformed control and A-T cell lines, both before and after irradiation. In combination, these results support the contention that the defective repair of DSB is a mechanism of the hypersensitivity linked to the A-T mutation.