Sister Chromatid Exchanges, Chromosomal Aberrations, and Cytotoxicity Produced by Antitumor Topoisomerase II Inhibitors in Sensitive (DC3F) and Resistant (DC3F/9-OHE) Chinese Hamster Cells

Yves Pommier, Donna Kerrigan, Joseph M. Covey, Chien Song Kao-Shan, Jacqueline Whang-Peng

研究成果: 雜誌貢獻文章同行評審

77 引文 斯高帕斯(Scopus)

摘要

4’(9-Acridinylamino)methanesulfon-m-anisidide etoposide, and 2-methyl-9-hydroxyellipticinium are antitumor topoisomerase II (topo II) inhibitors. The relationship between drug-induced sister chromatid exchanges (SCEs) or chromosomal aberrations and cytotoxicity was investigated in Chinese hamster cells sensitive (DC3F) and resistant (DC3F/ 9-OHE) to topo II inhibitors. Thirty-min drug treatments produced SCEs and chromosomal aberrations in sensitive (DC3F) cells, 4’-(9-acridin-ylamino)methanesulfon-m-anisidide being more potent than etoposide or 2-methyl-9-hydroxyellipticinium at equimolar concentrations. Comparable treatments of resistant (DC3F/9-OHE) cells did not produce chromosomal damage. The cytotoxicity of 4’-(9-Acridinylamino)-methanesulfon-m-anisidide was also greater than that of etoposide or 2-methyl-9-hydroxyellipticinium in DC3F cells, and no cytotoxicity was observed in DC3F/9-OHE at drug concentrations that produced more than two logs of cell kill in DC3F cells. A plot of cytotoxicity versus SCEs showed a good correlation between the two parameters. Therefore, short treatments of mammalian cells with topo II inhibitors produce reversible topo II-mediated DNA breaks which are associated with chromosomal aberrations and SCEs whose number correlates with cytotoxicity. In addition, topo II mutant DC3F/9-OHE cells were more sensitive than DC3F cells to the chromosomal, DNA cross-linking and cytotoxic effects of mitomycin C and were equally sensitive to the cytotoxic effect of camptothecin.
原文英語
頁(從 - 到)512-516
頁數5
期刊Cancer Research
48
發行號3
出版狀態已發佈 - 一月 1 1988
對外發佈Yes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

指紋 深入研究「Sister Chromatid Exchanges, Chromosomal Aberrations, and Cytotoxicity Produced by Antitumor Topoisomerase II Inhibitors in Sensitive (DC3F) and Resistant (DC3F/9-OHE) Chinese Hamster Cells」主題。共同形成了獨特的指紋。

引用此