Adriamycin-Induced DNA Damage Mediated by Mammalian DNA Topoisomerase II

作者：K M Tewey, Thomas C. Rowe, Liu Yang, Brian D. Halligan, Leroy F. Liu · 发表于：Science · 年份：1984 · DOI：10.1126/science.6093249 · 被引用次数：1551 · 研究领域：Cancer therapeutics and mechanisms、Bioactive Compounds and Antitumor Agents、Synthesis and Biological Evaluation

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 and VM-26), adriamycin has been shown to induce single- and double-strand breaks in DNA. These strand breaks are 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 adriamycin and other related antitumor drugs.