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阿霉素和玫瑰树碱引起的脱氧核糖核酸损伤的修复

Repair of deoxyribonucleic acid lesions caused by adriamycin and ellipticine.

作者信息

Ross W E, Smith M C

出版信息

Biochem Pharmacol. 1982 May 15;31(10):1931-5. doi: 10.1016/0006-2952(82)90500-7.

Abstract

The intercalating agents adriamycin and ellipticine caused DNA single and double strand breaks and DNA-protein crosslinks in mammalian cells. Ellipticine caused a much higher frequency of each of these lesions than adriamycin, at equitoxic doses. However, adriamycin-induced DNA effects were slowly and incompletely repaired over 24 hr after drug removal while the effects of ellipticine were virtually completely repaired within 30 min. Repair of ellipticine-induced lesions was observed only if cells were diluted ( 100-fold) after drug treatment, suggesting that significant amounts of drug may have been sequestered in the cellular membranes. Cell dilution did not alter the effects of adriamycin. Removal of the DNA lesions was temperature dependent. Finally, the similarity in the rates of repair for DNA single and double strand breaks and DNA-protein crosslinks supports the hypothesis that they are functionally related.

摘要

嵌入剂阿霉素和玫瑰树碱可导致哺乳动物细胞中的DNA单链和双链断裂以及DNA-蛋白质交联。在等毒性剂量下,玫瑰树碱引起的这些损伤的频率比阿霉素高得多。然而,阿霉素诱导的DNA效应在药物去除后24小时内修复缓慢且不完全,而玫瑰树碱的效应在30分钟内几乎完全修复。仅当药物处理后细胞稀释(100倍)时,才观察到玫瑰树碱诱导损伤的修复,这表明大量药物可能已被隔离在细胞膜中。细胞稀释不会改变阿霉素的效应。DNA损伤的去除取决于温度。最后,DNA单链和双链断裂以及DNA-蛋白质交联的修复速率相似,支持了它们在功能上相关的假设。

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