INDUCTION AND REJOINING OF DNA DOUBLE-STRAND BREAKS AND INTERPHASE CHROMOSOME BREAKS AFTER EXPOSURE TO X-RAYS IN ONE NORMAL AND 2 HYPERSENSITIVE HUMAN FIBROBLAST CELL-LINES
INDUCTION AND REJOINING OF DNA DOUBLE-STRAND BREAKS AND INTERPHASE CHROMOSOME BREAKS AFTER EXPOSURE TO X-RAYS IN ONE NORMAL AND 2 HYPERSENSITIVE HUMAN FIBROBLAST CELL-LINES
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DOI：
10.2307/3579232
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发表时间：
1995-10-01
影响因子：
3.4
通讯作者：
MALAISE, EP
中科院分区：
文献类型：
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作者：
BADIE, C;ILIAKIS, G;MALAISE, EP
这项工作的目的是同时和定量地测量双链断裂（DSBs），间期染色体断裂和细胞致命性，无论是在照射后立即，或在此后的不同时间（长达24小时），在三种具有广泛不同内在辐射敏感性的未转化的人成纤维细胞系的细胞中。我们希望在DNA和染色体水平上评估初始损伤、修复动力学和残余损伤，并将这些参数与细胞杀伤联系起来。我们使用了HF19细胞（一种正常成纤维细胞系）、AT2细胞（一种来自共济失调毛细血管扩张症（AT）患者的放射敏感细胞系）和180BR细胞（一种来自无AT临床症状患者的放射敏感细胞系）。与HF19细胞相比，AT2和180BR细胞除了对辐射敏感外，还显示出修复潜在致命损伤的能力降低。通过脉冲场凝胶电泳测量，dsb的产量在所有三种细胞系中都是相似的（斜率对应于1.6-1.7% Gy(-1) dna相关放射性从凝胶孔释放到车道）。相比之下，HF19细胞照射24 h后的残余DSBs几乎为零（0.1%置信区间= 0-1.4%），而AT2和180BR细胞照射后立即测量的残余DSBs分别为12.5%（+/-2.3%）和43.8%（+/-1.2%）。辐照后，HF19、AT2和180BR细胞间期染色体残断率分别为11.6%（+/-1.6%）、29.7%（+/-5.7%）和41.4%（+/-2.2%）。DSBs的初始产量和过量间期染色体断裂量都不能解释三种细胞系放射敏感性的差异；然而，残差DSB、24 h时DSB再连接率、残差间期染色体断裂与细胞存活率之间存在相关性。(C) 1995年，辐射研究学会
The aim of this work was to measure simultaneously and in a quantitative manner double-strand breaks (DSBs), interphase chromosome breaks and cell lethality either immediately after irradiation, or at various times thereafter (up to 24 h), in cells of three nontransformed human fibroblast cell lines of widely different intrinsic radiosensitivity. We wished to assess initial damage, repair kinetics and residual damage at the DNA and the chromosome level, and to correlate these parameters with cell killing. We employed HF19 cells, a normal fibroblast cell line, AT2 cells, a radiosensitive cell line from a patient suffering from ataxia telangiectasia (AT), and 180BR cells, a radiosensitive cell line from a patient with no clinical symptoms of AT. AT2 and 180BR cells, in addition to being radiosensitive, also display a reduced ability to repair potentially lethal damage compared to HF19 cells. The yield of DSBs, as measured by pulsed-field gel electrophoresis, is similar in all three cell Lines (slopes correspond to 1.6-1.7% Gy(-1) of DNA-associated radioactivity released from the gel well into the lane). In contrast, residual DSBs measured 24 h after irradiation are almost zero for HF19 cells (0.1% confidence interval = 0-1.4%), but are 12.5% (+/-2.3%) and 43.8% (+/-1.2%) of those measured immediately after irradiation in AT2 and 180BR cells, respectively. Residual interphase chromosome breaks are 11.6% (+/-1.6%), 29.7% (+/-5.7%) and 41.4% (+/-2.2%) of those measured immediately after irradiation in HF19, AT2 and 180BR cells, respectively. Neither the initial yield of DSBs nor that of excess interphase chromosome breaks can explain the differences in radiosensitivity between the three cell lines; however, there is a correlation between residual DSBs, rate of DSB rejoining at 24 h, residual interphase chromosome breaks on the one hand and cell survival on the other hand. (C) 1995 by Radiation Research Society