Gierthy J F, Lincoln D W, Kampcik S J, Dickerman H W, Bradlow H L, Niwa T, Swaneck G E
Wadsworth Center for Laboratories & Research, New York State Department of Health, Albany 12201-0509.
Biochem Biophys Res Commun. 1988 Dec 15;157(2):515-20. doi: 10.1016/s0006-291x(88)80279-1.
2,3,7,8-Tetrachlorodibenzo-p-dioxin exhibits antiestrogenic activity and induces cytochromes P-450 in estrogen-dependent MCF-7 human breast-cancer cells. To determine whether induction of 2- or 16 alpha-hydroxylation of 17 beta-estradiol has a role in this antiestrogenic activity, MCF-7 cells which were exposed to this xenobiotic for 72 hrs were incubated with either [2-3H] or [16 alpha-3H] 17 beta-estradiol and the extent of tritiated H2O formation, indicative of site-specific hydroxylation, was determined. 2,3,7,8-Tetrachlorodibenzo-p-dioxin-treated MCF-7 cultures showed an 8-fold increase in 2-hydroxylation and a 2-fold increase in 16 alpha-hydroxylation. These results support the suggestion that increased hydroxylation of 17 beta-estradiol may have a role in the antiestrogenic activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in MCF-7 cells.
2,3,7,8-四氯二苯并-对-二恶英具有抗雌激素活性,并能在雌激素依赖性的MCF-7人乳腺癌细胞中诱导细胞色素P-450。为了确定17β-雌二醇的2-或16α-羟基化诱导是否在这种抗雌激素活性中起作用,将暴露于这种外源性物质72小时的MCF-7细胞与[2-³H]或[16α-³H]17β-雌二醇一起孵育,并测定作为位点特异性羟基化指标的氚化水形成程度。经2,3,7,8-四氯二苯并-对-二恶英处理的MCF-7培养物显示2-羟基化增加了8倍,16α-羟基化增加了2倍。这些结果支持了这样的观点,即17β-雌二醇羟基化增加可能在2,3,7,8-四氯二苯并-对-二恶英对MCF-7细胞的抗雌激素活性中起作用。