DNA DOUBLE-STRAND BREAKS IN MAMMALIAN-CELLS AFTER EXPOSURE TO INTERCALATING AGENTS
DNA DOUBLE-STRAND BREAKS IN MAMMALIAN-CELLS AFTER EXPOSURE TO INTERCALATING AGENTS
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DOI：
10.1016/0005-2787(81)90145-3
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发表时间：
1981-01-01
期刊：
影响因子：
--
通讯作者：
BRADLEY, MO
中科院分区：
文献类型：
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作者：
ROSS, WE;BRADLEY, MO
将小鼠[白血病] L1210细胞暴露于嵌入剂，如[抗肿瘤药物]阿霉素，椭圆树碱和放线菌素D，导致DNA单链断裂和DNA-蛋白质交联。为了进一步表征这些药物与细胞内DNA之间的相互作用，采用了改进的碱性洗脱技术。其允许检测DNA双链断裂。椭圆霉素（1.25-5.0 μ g/ml）、阿霉素（0.5-3.0 μ g/ml）和放线菌素D（1.5-3.0 μ g/ml）在处理1小时后均引起来自L1210细胞的DNA的双链断裂。对于椭圆藤碱，每单链断裂发现的双链断裂数最高，尽管这是3种药物中细胞毒性最小的。通过比较辐射引起的单链和双链断裂频率与椭圆树碱引起的频率，似乎观察到的大多数（如果不是全部）药物诱导的单链断裂实际上代表双链断裂。这些双链断裂可能是由于细胞内酶的作用，可能是拓扑异构酶，它会同时断裂两条链，以减轻药物嵌入引起的拓扑应变。
Exposing mouse [leukemia] L1210 cells to intercalating agents such as [the antineoplastic drugs] adriamycin, ellipticine and actinomycin D results in DNA single-strand breaks and DNA-protein crosslinks. To characterize further the interaction between these drugs and intracellular DNA, a modification of the alkaline elution technique was employed. which allows the detection of DNA double-strand breaks. Ellipticine (1.25-5.0 .mu.g/ml), adriamycin (0.5-3.0 .mu.g/ml) and actinomycin D (1.5-3.0 .mu.g/ml) all caused double-strand breaks in DNA from L1210 cells following a 1 h treatment. The number of double-strand breaks found per single strand break was highest for ellipticine, despite the fact that this is the least cytotoxic of the 3 drugs. By comparing the single and double strand break frequency caused by radiation to that caused by ellipticine, it appears that most if not all of the drug-induced single strand breaks observed actually represent double-strand breaks. These double-strand breaks may result from the action of an intracellular enzyme, perhaps topoisomerase, which breaks both strands in concert to relieve the topologial strain caused by drug intercalation.