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, ...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.展开更多
基金supported by the National Natural Science Foundation of China (Nos. 21407168, 21377142 and 21477146)the Young Scientists Fund of RCEES (No. RCEES-QN-20130004F)Chinese Academy of Sciences (Nos. XDB14040100 and YSW2013A01)
文摘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.
