摘要
Camptothecin, a plant alkaloid with antitumor activity, has been shown to be a potent inhibitor of nucleic acid synthesis and a strong inducer of DNA strand breaks in mammalian cells. Previous studies have shown that camptothecin inhibits purified mammalian DNA topoisomerase I by trapping a reversible enzyme-DNA “cleavable complex” (Hsiang et al., J. Biol. Chem., 260: 14873–14878, 1985). Our present studies, using L1210 cells and SV40-infected monkey cells, have shown that campto-thedn-induced strand breaks are protein linked. The linked protein is most likely DNA topoisomerase I as revealed by immunoblot analysis, using antibodies against purified mammalian DNA topoisomerase I. Brief heating of camptothecin-treated cells to 65°C resulted in a rapid reduction of the number of protein-linked DNA breaks. Reversal of the camptotheScin-induced topoisomerase I-DNA complex by heat was also observed in an in vitro system by using purified mammalian DNA topoisomerase I. Our results suggest that camptothecin interferes with DNA topoisomerase I both in cultured mammalian cells and in the purified system by trapping a reversible enzyme-DNA cleavable complex.
原文 | 英語 |
---|---|
頁(從 - 到) | 1722-1726 |
頁數 | 5 |
期刊 | Cancer Research |
卷 | 48 |
發行號 | 7 |
出版狀態 | 已發佈 - 1988 |
對外發佈 | 是 |
ASJC Scopus subject areas
- 腫瘤科
- 癌症研究