ABSTRACT

Triclosan (TCS) is an antibacterial and antifungal agent used in many consumer products and exhibits a chemical structure similar to non-steroidal estrogen, which is known to induce endocrine disruption. Triclosan has been found in human plasma, urine, and breast milk, and the safety of TCS-containing products has been disputed. Although studies attempted to determine the estrogenic activity of TCS, no clear results have emerged. The aim of the present study was to examine estrogenic activity of TCS using an in vitro E-screen assay and an in vivo uterotrophic assay. The in vitro E-screen assay demonstrated that TCS significantly enhanced proliferation of MCF-7 breast cancer cells, although not in a concentration-dependent manner. The in vivo uterotrophic results showed no significant change in the weight of uteri obtained from TCS-administered Sprague-Dawley rats. Further, to understand the estrogenic activity attributed to TCS at the molecular level, gene-expression profiling of uterus samples was performed from both TCS- or estrogen-treated rats and the genes and cellular processes affected by TCS or estrogen were compared. Data demonstrated that both the genes and cellular processes affected by TCS or estrogen were significantly similar, indicating the possibility that TCS-mediated estrogenic activity occurred at the global transcriptome level. In conclusion, in vitro and gene-profiling results suggested that TCS exhibited estrogenic activity.

摘要

三氯生 (TCS) 是一种抗菌剂和抗真菌剂，用于许多消费品，其化学结构类似于非甾体雌激素，众所周知，非甾体雌激素会导致内分泌紊乱。三氯生已在人体血浆、尿液和母乳中发现，含TCS产品的安全性存在争议。尽管研究试图确定 TCS 的雌激素活性，但尚未出现明确的结果。本研究的目的是使用体外电子筛选试验和体内促子宫试验检测TCS 的雌激素活性。在体外E-屏幕测定表明TCS显著增强MCF-7乳腺癌细胞的增殖，虽然不是以依赖浓度的方式。在体内子宫营养结果显示从 TCS 给药的 Sprague-Dawley 大鼠获得的子宫重量没有显着变化。此外，为了在分子水平上了解归因于 TCS 的雌激素活性，对来自 TCS 或雌激素治疗的大鼠的子宫样本进行基因表达分析，并比较了受 TCS 或雌激素影响的基因和细胞过程。数据表明，受 TCS 或雌激素影响的基因和细胞过程均显着相似，表明 TCS 介导的雌激素活性可能发生在全球转录组水平。总之，体外和基因分析结果表明 TCS 表现出雌激素活性。