Huang Hongyu, Du Guizhen, Zhang Wei, Hu Jialei, Wu Di, Song Ling, Xia Yankai, Wang Xinru
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
J Appl Toxicol. 2014 Sep;34(9):1060-7. doi: 10.1002/jat.3012. Epub 2014 Apr 16.
Triclosan (TCS) and triclocarban (TCC), as broad spectrum antibacterial agents, are distributed widely in the environment and humans. Most studies have focused on their distribution and biodegradation, but the endocrine-disrupting effects of these chemicals, especially their estrogenic effects, are still unclear. In the present study, we investigated the estrogenic effects of TCS and TCC using a series of in vitro assays, including the ER reporter gene assay in the CV-1 cells, E-screen assay and evaluation of estrogen-responsive genes in the MCF-7 cells. The tested concentrations of TCS and TCC were both from 1 × 10(-9) to 1 × 10(-6) M. Results showed that TCS and TCC exerted estrogenic activities by inducing luciferase activities in an ER reporter gene assay, promoting the proliferation of the MCF-7 cells, up-regulating the expression of pS2 and down-regulating ERα expression at both the mRNA and protein levels in the MCF-7 cells. We further found that TCS and TCC could alter the expression of multiple microRNAs (mir-22, mir-206 and mir-193b) in the MCF-7 cells, which would help understand the mechanisms of their estrogenic effects on regulating the expression of ERα. In brief, our results demonstrated the potential estrogenic effects and profiled in vitro data for further risk assessment of TCS and TCC.
三氯生(TCS)和三氯卡班(TCC)作为广谱抗菌剂,在环境和人体中广泛分布。大多数研究集中在它们的分布和生物降解方面,但是这些化学物质的内分泌干扰效应,尤其是它们的雌激素效应,仍不清楚。在本研究中,我们使用了一系列体外试验来研究TCS和TCC的雌激素效应,包括CV-1细胞中的雌激素受体(ER)报告基因试验、E-筛选试验以及MCF-7细胞中雌激素反应基因的评估。TCS和TCC的测试浓度均为1×10⁻⁹至1×10⁻⁶ M。结果表明,在ER报告基因试验中,TCS和TCC通过诱导荧光素酶活性发挥雌激素活性,促进MCF-7细胞增殖,上调pS2的表达,并在mRNA和蛋白质水平下调MCF-7细胞中ERα的表达。我们进一步发现,TCS和TCC可改变MCF-7细胞中多种微小RNA(mir-22、mir-206和mir-193b)的表达,这将有助于理解它们对ERα表达调控的雌激素效应机制。简而言之,我们的结果证明了TCS和TCC潜在的雌激素效应,并提供了体外数据以进行进一步的风险评估。