Cell Proliferation Kinetics of MCF-7 Human Mammary Carcinoma Cells in Culture and Effects of Tamoxifen on Exponentially Growing and Plateau-Phase Cells

摘要: MCF-7 human mammary carcinoma cells were inoculated into 150-sq cm flasks at 3 X 10(5) cells/flask, and after a lag period of about 48 hr, these grew exponentially for 5 days with mean population doubling time 24 hr. During exponential growth, 80 to 90% in the "rapidly cycling" pool, clonogenic fraction was 50 60%, percentage G0-G1, S, G2 + M phases cell cycle 48.9 +/- 0.6% (S.E.), 39.4 0.6%, 11.6 0.3%, respectively. These parameters changed rapidly between Days 7 13 when plateau phase reached. Between 18, 74.8 0.7% 15.3 0.4% 9.8 phase. Only 30% cycling rapidly, had fallen less than 10%. Tamoxifen induced dose-dependent decrease growth rate growing cells, which accompanied by increase G0-G1-phase decline S-phase cells. At doses greater or equal 10 microM, 24-hr pulse tamoxifen cytotoxic Plateau-phase sensitive effects tamoxifen. In an attempt define kinetic basis G0-G1 accumulation tamoxifen, asynchronous pretreated 42 hr various efflux from assessed blocking their reentry G1 ICRF 159. Following treatment control cultures 159, two populations distinguished rates The majority left t1/2 2.3 ("rapidly cells). However, 18% much slower exit 30 ("slowly Pretreatment resulted proportion slow transit times. Although this appeared be predominant effect, also decreased slowly traversed G1. Simultaneous estradiol returned values partially reversed effect 7.5 microM but without on arrest progression It is concluded that accumulate following due expense appear relatively uninfluenced drug.