Effects of tamoxifen on cell cycle progression of synchronous MCF-7 human mammary carcinoma cells.
Effects of tamoxifen on cell cycle progression of synchronous MCF-7 human mammary carcinoma cells.
复制标题
DOI：
--
复制
发表时间：
1983-09
期刊：
影响因子：
11.2
通讯作者：
I. Taylor;P. Hodson;M. Green;R. Sutherland
中科院分区：
文献类型：
--
作者：
I. Taylor;P. Hodson;M. Green;R. Sutherland
三苯氧胺对细胞周期进程和克隆形成存活的影响已经使用MCF-7人乳腺癌细胞的同步培养物进行了研究。有丝分裂选择诱导细胞同步化。随后使用DNA流式细胞术进行的细胞周期分析显示，85%的同步化细胞的平均细胞周期时间为21.3小时，G 0-G1期平均持续时间为9小时，S期为9.3小时，G2 + M期为3小时。还观察到占总种群15%的缓慢循环或非循环亚群。暴露于他莫昔芬（5至12.5 μ M）导致通过G 0-G1和进入S期的细胞数量呈剂量依赖性减少。然而，那些未保留在G 0-G1期的细胞似乎以仅略低于未处理对照组的速率穿越G 0-G1期和细胞周期的其余部分。进一步的实验表明，在细胞周期进展的抑制和药物细胞毒性方面，对他莫昔芬的主要敏感性仅限于G 0-G1中期的短时间间隔。这2至4小时的最大药物敏感性期开始约4小时后，有丝分裂的选择，与药物暴露在此时间范围外有显着较少的影响。根据以前的研究与异步群体的MCF-7细胞这些观察结果的意义进行了讨论。
The effects of tamoxifen on cell cycle progression and clonogenic survival have been examined using synchronized cultures of MCF-7 human mammary carcinoma cells. Cell synchrony was induced by mitotic selection. Subsequent cell cycle analyses, using DNA flow cytometry, showed that 85% of synchronized cells had a mean cell cycle time of 21.3 hr with mean phase durations of 9 hr for G0-G1, 9.3 hr for S, and 3 hr for G2 + M. A slowly cycling or noncycling subpopulation comprising 15% of the total population was also observed. Exposure to tamoxifen (5 to 12.5 microM) resulted in a dose-dependent reduction in the number of cells progressing through G0-G1 and entering S phase. Those cells which were not retained in G0-G1, however, appeared to traverse G0-G1 and the remainder of the cell cycle at a rate only slightly less than that of untreated controls. Further experiments demonstrated that the major sensitivity to tamoxifen in terms of both inhibition of cell cycle progression and drug cytotoxicity was restricted to a short interval in the middle of G0-G1. This 2- to 4-hr period of maximum drug sensitivity began approximately 4 hr after mitotic selection, with drug exposures outside this time frame having markedly fewer effects. The significance of these observations in the light of previous studies with asynchronous populations of MCF-7 cells is discussed.