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题名: In vitro assessment of thyroid hormone receptor activity of four organophosphate esters
作者: Ren, Xiaomin; Cao, Linying; Yang, Yu; Wan, Bin; Wang, Sufang; Guo, Lianghong
刊名: JOURNAL OF ENVIRONMENTAL SCIENCES
出版日期: 2016-07
卷号: 45, 期号:0, 页码:185-190
关键词: organophosphate esters ; disruption effect ; TDCPP ; TR pathway ; agonistic activity
DOI: 10.1016/j.jes.2015.12.021
部门归属: 环境化学与生态毒理学国家重点实验室
英文摘要: Previous animal experiments have implied that organophosphate esters (OPEs) have a disruption effect on the thyroid endocrine system. However, knowledge of the toxicological mechanism remains limited. In this study, the activities of four OPEs have been characterized against the thyroid hormone (TH) nuclear receptor (TR) using two in vitro models, with the aim of evaluating their toxicity mechanisms towards the TR. The results of a TH-dependent cell proliferation assay showed that h.-is (2-chloro-1-(chloromethyl)ethyl)phosphate (TDCPP) could induce cell growth, while the other three OPEs had no effect. The results of a luciferase reporter gene assay revealed that all four of the OPEs tested in the current study showed agonistic activity towards TR4, with TDCPP being the most potent one. Moreover, molecular docking revealed that all the tested OPEs could fit into the ligand binding pocket of TR4, with TDCPP binding more effectively than the other three OPEs. Taken together, these data suggest that OPEs might disrupt the thyroid endocrine system via a mechanism involving the activation of TR. (C) 2016 The Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier E.V.
收录类别: SCI
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内容类型: 期刊论文
URI标识: http://ir.rcees.ac.cn/handle/311016/35874
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