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Thyroid hormone disrupting effects of organophosphorus flame retardants and its mechanisms of action, take TCPP as an example |
SHEN Yang, YU Chang, KONG Dong-dong, WANG Rong-fang, LI Jian |
Engineering Research Center of Groundwater Pollution Control and Remediation, Ministry of Education, College of Water Sciences, Beijing Normal University, Beijing 100875, China |
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Abstract In the present study, typical organophosphorus flame retardants (OPFRs), tris (2-chloropropyl) phosphate (TCPP), was selected as the object of study. GH3 cell proliferation assay was used to test the thyroid disrupting activity of TCPP; a two-hybrid thyroid receptor (TR) yeast assay, GH3 (TRβ-) cell proliferation assay and real time quantitative PCR were used to investigate the mechanism of action. The results revealed that TCPP decreased the GH3 cell proliferation at concentrations ranging from 1×10-4mol/L to 2×10-4mol/L. Furthermore, the results from two-hybrid TR yeast assay and GH3(TRβ-) cell proliferation assay suggested that TCPP could disrupt thyroid hormone activity through genomic and non-genomic pathway. The results of real time quantitative PCR supported the mRNA expression levels of c-fos, TRβ, integrin-av and k-ras were inhibited, suggesting that TCPP might induce thyroid hormone disruption by adjusting TRβ gene expression and activating αvβ3-ERK-1/2 signaling pathway. All of these results could provide the basic data and theoretical support for the environmental risk assessment of TCPP.
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Received: 23 October 2017
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Corresponding Authors:
李剑,副教授,lijian@bnu.edu.cn
E-mail: lijian@bnu.edu.cn
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