Deficiency in DNA repair in mouse lymphoma strain L5178Y-S.
Deficiency in DNA repair in mouse lymphoma strain L5178Y-S.
复制标题
小鼠淋巴瘤株 L5178Y-S 的 DNA 修复缺陷。
DOI：
10.1073/pnas.84.21.7562
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发表时间：
1987
影响因子：
11.1
通讯作者：
Horng,MF
中科院分区：
文献类型：
--
作者：
Evans,HH;Ricanati,M;Horng,MF
辐射诱导的DNA损伤的生产和修复进行了测量过滤器洗脱小鼠淋巴瘤L5178 Y细胞株不同的敏感性电离辐射。通过在pH 12.1、9.6和7.2下的过滤洗脱测量的辐射诱导损伤的诱导在抗性菌株LY-R和敏感菌株LY-S中是相似的。单链断裂和碱不稳定位点的修复，在照射后的不同时间在pH 12.1下通过过滤器洗脱测量，在菌株LY-S中比在菌株LY-R中稍微慢一些，尽管在20分钟的修复期后，修复的程度在两种菌株中是相等的。然而，当在pH 9.6或pH 7.2下进行过滤器洗脱时，X-辐射诱导的损伤的修复在菌株LY-S中比在菌株LY-R中广泛得多。我们假设pH 9.6下的过滤器洗脱程度是直接双链断裂以及紧密相对的单链断裂和pH 9.6不稳定位点（及其组合）发生的量度，并且pH 7.2下的洗脱程度是单独直接双链断裂发生的量度。如果这些假设是正确的，结果表明，菌株LY-S的电离辐射的细胞毒性效应的敏感性是由该菌株修复坦率的双链断裂和pH 9.6不稳定的病变的能力不足。pH 9.6不稳定的病变的修复是温度敏感的菌株LY-S，如以前发现的细胞恢复过程中，这种菌株。两个独立的耐辐射的菌株LY-S的变种，分离后，长期暴露的LY-S细胞低剂量率辐射，表现出缺陷的修复pH 9.6不稳定的病变中观察到的菌株LY-S。然而，坦率的双链断裂的修复是更广泛的抗辐射的变种比菌株LY-S和类似的程度发生在菌株LY-R后60分钟postirradiation孵育。结果表明，在pH 9.6与pH 7.2下通过过滤器洗脱测量的DNA损伤的性质存在差异，并且在耐辐射变体的情况下，pH 9.6不稳定病变的修复缺陷不会导致细胞致死。与菌株LY-S相比，这些变体的辐射抗性可能至少部分是由于恢复了重新连接坦率的DNA双链断裂的能力。
The production and repair of radiation-induced DNA damage were measured by filter elution in strains of mouse lymphoma L5178Y cells differing in their sensitivity to ionizing radiation. The induction of radiation-induced damage, as measured by filter elution at pH 12.1, 9.6, and 7.2, was similar in the resistant strain LY-R and the sensitive strain LY-S. The repair of single-strand breaks and alkali-labile sites, as measured by filter elution at pH 12.1 at various times after irradiation, was somewhat slower in strain LY-S than in strain LY-R, although after a 20-min repair period the extent of repair was equal in the two strains. However, when filter elution was performed at either pH 9.6 or pH 7.2, the repair of x-radiation-induced damage was much less extensive in strain LY-S than in strain LY-R. We have assumed that the extent of filter elution at pH 9.6 is a measure of the occurrence of frank double-strand breaks as well as closely opposing single-strand breaks and pH 9.6-labile sites (and combinations thereof), and that the extent of elution at pH 7.2 is a measure of the occurrence of frank double-strand breaks alone. If these assumptions are correct, the results suggest that the sensitivity of strain LY-S to the cytotoxic effects of ionizing radiation is caused by a deficiency in the ability of this strain to repair frank double-strand breaks and pH 9.6-labile lesions. The repair of pH 9.6-labile lesions was temperature sensitive in strain LY-S, as previously found for cellular recovery processes in this strain. Two independent radiation-resistant variants of strain LY-S, isolated after protracted exposure of LY-S cells to low-dose-rate radiation, showed a deficiency in the repair of pH 9.6-labile lesions similar to that observed in strain LY-S. However, the repair of frank double-strand breaks was more extensive in the radiation-resistant variants than in strain LY-S and was similar in extent to that occurring in strain LY-R after a 60-min postirradiation incubation. The results suggest that there is a difference in the nature of DNA damage measured by filter elution at pH 9.6 vs. pH 7.2 and that a deficiency in the repair of pH 9.6-labile lesions does not contribute to cell lethality in the case of the radiation-resistant variants. The radiation resistance of these variants in comparison to strain LY-S may be due at least in part to recovery of the ability to rejoin frank DNA double-strand breaks.