title: In vitro assessment of thyroid hormone receptor activity of four organophosphate esters.
abstract: 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 tris(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 TRβ, with TDCPP being the most potent one. Moreover, molecular docking revealed that all the tested OPEs could fit into the ligand binding pocket of TRβ, 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.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China. Electronic address: xmren@rcees.ac.cn.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Linying
authors.initials: L
authors.lastname: Cao
authors.affiliation: State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Eco-toxicology, Research Centre for Eco-environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Institute of Environment and Health, Jianghan University, Wuhan 430056, China. Electronic address: LHGuo@rcees.ac.cn.
authors.forename: Lianghong
authors.initials: L
authors.lastname: Guo
mesh_terms: D001681:Biological Assay; D004952:Esters / Q000633:toxicity*; D015386:Hazardous Substances / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000633:toxicity*; D011988:Receptors, Thyroid Hormone; D018675:Toxicity Tests
chemical_list: D004952:Esters; D015386:Hazardous Substances; D009943:Organophosphorus Compounds; D011988:Receptors, Thyroid Hormone
keywords: TDCPP; TR pathway; agonistic activity; disruption effect; organophosphate esters