DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II

T. C. Rowe, G. L. Chen, Y. H. Hsiang, Leroy-Fong Liu

研究成果: 雜誌貢獻文章

235 引文 斯高帕斯(Scopus)

摘要

Antitumor drugs from many chemical classes have been shown to induce protein-linked DNA breaks in cultured mammalian cells and in vitro in the presence of purified mammalian DNA topoisomerase II. The possibility that mammalian DNA topoisomerase II is an intracellular target which mediates drug-induced DNA breaks is supported by the following studies using 4'-(9-acridinylamino)methane-sulfon-m-anisidide (m-AMSA): (a) a single m-AMSA-dependent DNA cleavage activity copurified with calf thymus DNA topoisomerase II activity at all chromatographic steps of the enzyme purification; (b) m-AMSA-induced DNA cleavage by this purified activity resulted in the covalent attachment of protein to the 5'-ends of the DNA via a tyrosyl phosphate bond. This covalently linked protein has the same reduced molecular weight as purified calf thymus DNA topoisomerase II. The possibility that topoisomerase II-mediated DNA breaks may be responsible for cytotoxicity has also been investigated using a number of m-AMSA-related acridines. The level of topoisomerase II-mediated DNA breaks in vitro strongly correlates with the level of protein-linked DNA breaks in cultured cells and drug-induced cytotoxicity. These results suggest that mammalian DNA topoisomerase II may be a cytotoxic target of antitumor acridines.

原文英語
頁(從 - 到)2021-2026
頁數6
期刊Cancer Research
46
發行號4 II
出版狀態已發佈 - 1986
對外發佈Yes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

指紋 深入研究「DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II」主題。共同形成了獨特的指紋。

  • 引用此

    Rowe, T. C., Chen, G. L., Hsiang, Y. H., & Liu, L-F. (1986). DNA damage by antitumor acridines mediated by mammalian DNA topoisomerase II. Cancer Research, 46(4 II), 2021-2026.