ADRIAMYCIN-INDUCED DNA DAMAGE MEDIATED BY MAMMALIAN DNA TOPOISOMERASE-II
ADRIAMYCIN-INDUCED DNA DAMAGE MEDIATED BY MAMMALIAN DNA TOPOISOMERASE-II
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DOI：
10.1126/science.6093249
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发表时间：
1984-01-01
期刊：
影响因子：
56.9
通讯作者：
LIU, LF
中科院分区：
文献类型：
--
作者：
TEWEY, KM;ROWE, TC;LIU, LF
阿霉素（阿霉素），一种有效的抗肿瘤药物在临床上使用，与核酸和细胞膜相互作用，但其抗肿瘤活性的分子基础是未知的。与许多嵌入性抗肿瘤药物和非嵌入性表鬼臼毒素（VP-16 [依托泊苷]、VM-26 [替尼泊苷]）相似，阿霉素可诱导DNA单链和双链断裂。这些链断裂是不寻常的，因为共价结合的蛋白质似乎与每个断裂的磷酸二酯键相关。在体外研究中，哺乳动物DNA拓扑异构酶II介导阿霉素和其他相关抗肿瘤药物对DNA的损伤。
Adriamycin (doxorubicin), a potent antitumor drug in clinical use, interacts with nucleic acids and cell membranes, but the molecular basis for its antitumor activity is unknown. Similar to a number of intercalative antitumor drugs and nonintercalative epipodophyllotoxins (VP-16 [etoposide], VM-26 [teniposide]), adriamycin was shown to induce single- and double-strand breaks in DNA. These strand breaks are in unusual because a covalently bound protein appears to be associated with each broken phosphodiester bond. In studies in vitro, mammalian DNA topoisomerase II mediates DNA damage by adriamyicn and other related antitumor drugs.