Department of Physiology and Toxicology of Reproduction, Chair of Animal Physiology, Institute of Zoology, Jagiellonian University, Kraków, Poland.
Environ Toxicol Pharmacol. 2008 Mar;25(2):227-33. doi: 10.1016/j.etap.2007.10.004. Epub 2007 Oct 22.
Certain estradiol metabolites and industrial pollutants, like polychlorinated biphenyls, may play a more important role in enhancing breast cancer risk than 17β-estradiol. The aim of this study was to compare the effects of 17β-estradiol (E2) with that of the air pollutant 4-chlorobiphenyl (PCB3) and four of their hydroxylated metabolites on cell cycle, proliferation, and apoptosis in MCF-7 human breast cancer cells at concentrations of 0.1-10nM (E2, 2-OH-E2, and 4-OH-E2) and 0.3-300nM (PCB3, 4-OH-PCB3, and 3, 4-diOH-PCB3) and 24-260h of exposure. E2 increased cell proliferation and cells in S-phase at all time points. 2-OH-E2 and 4-OH-E2 had no effect on the cell cycle, but a stimulatory action on cell proliferation from 72 to 260h of exposure to 4-OH-E2 and at 260h to 2-OH-E2 was seen. E2 and its metabolites had no effect on apoptosis. PCB3 and 4-OH-PCB3 showed no effect on proliferation, apoptosis or cell cycle distribution at any concentration and time point. Longer time exposures to 3,4-di-OH-PCB at 300nM caused a decrease of cells and an increase in G2/M and apoptotic cells. These results confirm the proliferative effect of E2 and its metabolite 4-OH-E2 in estrogen receptor positive breast cancer cells, but show no mitogenic activity for PCB3 and 4-OH-PCB3. However, the cell cycle and apoptosis effects of 3,4-diOH-PCB3 need further analysis.
某些雌二醇代谢物和工业污染物，如多氯联苯，可能比 17β-雌二醇在增强乳腺癌风险方面发挥更重要的作用。本研究旨在比较 17β-雌二醇（E2）与空气污染物 4-氯联苯（PCB3）及其四种羟基代谢物在 0.1-10nM（E2、2-OH-E2 和 4-OH-E2）和 0.3-300nM（PCB3、4-OH-PCB3 和 3,4-二 OH-PCB3）浓度以及 24-260 小时暴露时间对 MCF-7 人乳腺癌细胞周期、增殖和凋亡的影响。E2 增加了细胞增殖和所有时间点的 S 期细胞。2-OH-E2 和 4-OH-E2 对细胞周期没有影响，但在 4-OH-E2 暴露 72-260 小时和 260 小时时，对细胞增殖有刺激作用。E2 和其代谢物对凋亡没有影响。在任何浓度和时间点，PCB3 和 4-OH-PCB3 对增殖、凋亡或细胞周期分布均无影响。300nM 长时间暴露于 3,4-二-OH-PCB 会导致细胞减少，G2/M 和凋亡细胞增加。这些结果证实了 E2 及其代谢物 4-OH-E2 在雌激素受体阳性乳腺癌细胞中的增殖作用，但对 PCB3 和 4-OH-PCB3 没有促有丝分裂活性。然而，3,4-二 OH-PCB3 的细胞周期和凋亡作用需要进一步分析。
