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三氯生在乳腺癌细胞中的雌激素和雄激素活性。

Oestrogenic and androgenic activity of triclosan in breast cancer cells.

作者信息

Gee R H, Charles A, Taylor N, Darbre P D

机构信息

School of Biological Sciences, The University of Reading, Reading, RG6 6AJ, UK.

出版信息

J Appl Toxicol. 2008 Jan;28(1):78-91. doi: 10.1002/jat.1316.

Abstract

As a consequence of its widespread use as an antimicrobial agent in consumer goods, triclosan has become distributed ubiquitously across the ecosystem, and recent reports that it can cause endocrine disruption in aquatic species has increased concern. It is reported here that triclosan possesses intrinsic oestrogenic and androgenic activity in a range of assays in vitro which could provide some explanation for the endocrine disrupting properties described in aquatic populations. In terms of oestrogenic activity, triclosan displaced [(3)H]oestradiol from oestrogen receptors (ER) of MCF7 human breast cancer cells and from recombinant human ER alpha/ER beta. Triclosan at 10(-5) m completely inhibited the induction of the oestrogen-responsive ERE-CAT reporter gene in MCF7 cells by 10(-10) m 17beta-oestradiol and the stimulation of growth of MCF7 human breast cancer cells by 10(-10) m 17beta-oestradiol. On its own, 1 microm triclosan increased the growth of MCF7 cells over 21 days. Triclosan also had androgenic activity. It displaced [(3)H]testosterone from binding to the ligand binding domain of the rat androgen receptor (AR). Triclosan was able to inhibit the induction of the androgen-responsive LTR-CAT reporter gene in S115 mouse mammary tumour cells by 10(-9) m testosterone and in T47D human breast cancer cells by 10(-8) m testosterone at concentrations of 10(-7) m and 10(-6) m, respectively. Triclosan at 2 x 10(-5) m antagonized the stimulation of the growth of S115+A mouse mammary tumour cells by 10(-9) m testosterone. The finding that triclosan has oestrogenic and androgenic activity warrants further investigation in relation to both endocrine disruption of aquatic wildlife and any possible impact on human health.

摘要

由于三氯生作为抗菌剂在消费品中广泛使用,它已在生态系统中普遍分布,最近有报道称其会导致水生物种内分泌紊乱,这引发了更多关注。本文报道,三氯生在一系列体外试验中具有内在的雌激素和雄激素活性,这可为水生生物群体中所描述的内分泌干扰特性提供一些解释。就雌激素活性而言,三氯生从MCF7人乳腺癌细胞的雌激素受体(ER)以及重组人ERα/ERβ中取代了[³H]雌二醇。10⁻⁵m的三氯生完全抑制了10⁻¹⁰m 17β-雌二醇对MCF7细胞中雌激素反应性ERE-CAT报告基因的诱导以及10⁻¹⁰m 17β-雌二醇对MCF7人乳腺癌细胞生长的刺激。单独使用时,1μm的三氯生在21天内增加了MCF7细胞的生长。三氯生还具有雄激素活性。它从与大鼠雄激素受体(AR)的配体结合域的结合中取代了[³H]睾酮。在浓度分别为10⁻⁷m和10⁻⁶m时,三氯生能够抑制10⁻⁹m睾酮对S115小鼠乳腺肿瘤细胞中雄激素反应性LTR-CAT报告基因的诱导以及10⁻⁸m睾酮对T47D人乳腺癌细胞中该报告基因的诱导。2×10⁻⁵m的三氯生拮抗了10⁻⁹m睾酮对S115 + A小鼠乳腺肿瘤细胞生长的刺激。三氯生具有雌激素和雄激素活性这一发现,有必要就其对水生野生动物的内分泌干扰以及对人类健康的任何可能影响展开进一步研究。

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