A comparison of the induction of DNA double-strand breakage and lethal lesions by X irradiation in ataxia telangiectasia and normal fibroblasts.
A comparison of the induction of DNA double-strand breakage and lethal lesions by X irradiation in ataxia telangiectasia and normal fibroblasts.
复制标题
X 射线照射对共济失调毛细血管扩张和正常成纤维细胞诱导 DNA 双链断裂和致死损伤的比较。
作者：
I. Radford;G. Hodgson
各种证据表明，DNA双链断裂（DSB）是电离辐射引起的哺乳动物细胞杀伤的关键损伤（例如，（1,2））。我们已经提出，一般来说，诱导的DNA DSB水平可以预测细胞杀伤水平（3,4）。基于对辐射敏感的哺乳动物细胞系的研究，一些作者最近批评了这一假设，并提出DNA DSB修复动力学也是决定细胞杀伤水平的一个重要因素（57）。这些评论促使我们提出数据，比较DNA DSB诱导和细胞杀伤在x照射正常（IMR 90）和辐射敏感的失调性毛细血管扩张症（AT）人成纤维细胞，并指出我们的批评者提出的数据的其他解释。下面的讨论假设DNA DSB也是AT细胞的致死性病变。然而，仍有可能AT细胞在修复另一种DNA损伤类别的亚群方面存在缺陷。如前所述(3)，使用非变性过滤洗脱技术测量x照射的正常和AT成纤维细胞中的DNA DSB。关于IMR 90细胞的生长、放射性标记和克隆的细节已经在前面给出(4)。在细胞(通用汽车3487年从人类遗传变异细胞库,卡姆登,NJ)是生长在MEM加上20%胎牛血清的修改和人口倍增时间约30 h。接种15小时后,在细胞对DNA化验双边带孵化了[methyl-14C]胸苷(3 X 103 Bq / ml, 5点胸苷)在细胞克隆为大约30 h。90年IMR细胞(4),所述除了克隆菜肴孵化了枚举前17天。控制电镀效率从2%到5%不等。所有实验均采用指数生长细胞。
A variety of evidence indicates that DNA double-strand breakage (DSB) is the critical ionizing radiation-induced lesion responsible for mammalian cell killing (e.g., (1, 2)). We have suggested that, in general, the induced level of DNA DSB is predictive of the level of cell killing (3, 4). Based on studies using radiation-sensitive mammalian cell lines, several authors have recently criticized this postulate and have suggested that the kinetics of DNA DSB repair is also an important factor in determining the level of cell killing (57). These comments have prompted us to present data that compare DNA DSB induction and cell killing in X-irradiated normal (IMR 90) and radiation-sensitive ataxia telangiectasia (AT) human fibroblasts, and to point out other interpretations of the data presented by our critics. The following discussion assumes that DNA DSB is also the lethal lesion in AT cells. However, it remains a possibility that AT cells are defective in the repair of a subset of another DNA lesion category. The nondenaturing filter elution technique was used, as described previously (3), to measure DNA DSB in X-irradiated normal and AT fibroblasts. Details of the growth, radioactive labeling, and cloning of IMR 90 cells have been given previously (4). The AT cells (GM 3487A from the Human Genetic Mutant Cell Repository, Camden, NJ) were grown in the a-modification of MEM plus 20% fetal calf serum and had a population doubling time of around 30 h. Fifteen hours after subculturing, AT cells to be assayed for DNA DSB were incubated with [methyl-14C]thymidine (3 X 103 Bq/ml, 5 AM thymidine) for around 30 h. The AT cells were cloned as described for IMR 90 cells (4), except that cloning dishes were incubated for 17 days prior to enumeration. Control plating efficiencies ranged from 2 to 5%. Exponentially growing cells were used for all experiments.
小鼠淋巴瘤株 L5178Y-S 的 DNA 修复缺陷。
DOI：
10.1073/pnas.84.21.7562
发表时间：
1987
影响因子：
11.1
作者：
Evans,HH;Ricanati,M;Horng,MF
通讯作者：
Horng,MF
碘 125 对共济失调毛细血管扩张成纤维细胞的放射毒性。
DOI：
10.1016/0005-2787(81)90218-5
发表时间：
1981
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Ritter,MA
通讯作者：
Ritter,MA