Sister chromatid exchanges, chromosomal aberrations, and cytotoxicity produced by antitumor topoisomerase II inhibitors in sensitive (DC3F) and resistant (DC3F/9-OHE) Chinese hamster cells.
Sister chromatid exchanges, chromosomal aberrations, and cytotoxicity produced by antitumor topoisomerase II inhibitors in sensitive (DC3F) and resistant (DC3F/9-OHE) Chinese hamster cells.
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抗肿瘤拓扑异构酶 II 抑制剂在敏感 (DC3F) 和耐药 (DC3F/9-OHE) 中国仓鼠细胞中产生的姐妹染色单体交换、染色体畸变和细胞毒性。
作者：
Y. Pommier;D. Kerrigan;J. Covey;C. Kao;J. Whang
4‘-(9-Acridinylamino)methanesulfon-m-anisidide，、依托泊苷和2-甲基-9-羟基椭圆形是抗肿瘤拓扑异构酶II(TOPO II)的抑制剂。本文研究了药物诱导的姐妹染色单体互换(SCE)和染色体异常与Topo II抑制剂敏感(DC3F)和耐药(DC3F/9-OHE)中国仓鼠细胞毒性的关系。30min的药物处理在敏感的(DC3F)细胞中产生了SCE和染色体畸变，在等摩尔浓度下，4‘-(9-acridinylamino)methanesulfon-m-anisidide比依托泊苷或2-甲基-9-羟基椭圆形更有效。耐药(DC3F/9-OHE)细胞的类似处理没有产生染色体损伤。4‘-(9-Acridinylamino)-methanesulfon-m-anisidide对DC3F细胞的细胞毒作用也强于依托泊苷或2-甲基-9-羟基椭圆形，当药物浓度超过两个对数时，DC3F/9-OHE对DC3F细胞无细胞毒作用。细胞毒性与SCES的关系图显示，这两个参数之间有很好的相关性。因此，用Topo II抑制剂短期处理哺乳动物细胞会产生可逆的Topo II介导的DNA断裂，这与染色体异常和SCE有关，其数量与细胞毒性相关。此外，Topo II突变体DC3F/9-OHE细胞对丝裂霉素C的染色体、DNA交联和细胞毒作用比DC3F细胞更敏感，对喜树碱的细胞毒作用也同样敏感。
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-acridinylamino)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.
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DOI：
10.1073/pnas.81.5.1361
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
NELSON, EM;TEWEY, KM;LIU, LF
通讯作者：
LIU, LF
DOI：
10.1016/s0021-9258(17)47282-6
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
K. M. Tewey;G. L. Chen;E. Nelson;L. Liu
通讯作者：
K. M. Tewey;G. L. Chen;E. Nelson;L. Liu
DOI：
10.1016/s0021-9258(18)90729-5
发表时间：
1984-11
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
G. L. Chen;L. Yang;T. Rowe;B. Halligan;K. M. Tewey;L. Liu
通讯作者：
G. L. Chen;L. Yang;T. Rowe;B. Halligan;K. M. Tewey;L. Liu
细胞增殖和染色质构象对人脑肿瘤细胞和人成纤维细胞中嵌入剂诱导的蛋白质相关 DNA 裂解的影响。
影响因子：
11.2
作者：
Zwelling,LA;Estey,E;Silberman,L;Doyle,S;Hittelman,W
通讯作者：
Hittelman,W
DOI：
10.1073/pnas.81.9.2616
发表时间：
1984-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DINARDO, S;VOELKEL, K;STERNGLANZ, R
通讯作者：
STERNGLANZ, R