Polychlorinated Diphenylsulfides Activate Aryl Hydrocarbon Receptor 2 in Zebrafish Embryos: Potential Mechanism of Developmental Toxicity

文献类型： 外文期刊

第一作者： Zhang, Rui

作者： Zhang, Rui;Wang, Xiaoxiang;Wang, Xiaoxiang;Zhang, Xuesheng;Song, Chao;Song, Chao;Letcher, Robert J.;Letcher, Robert J.;Liu, Chunsheng

作者机构：

期刊名称：ENVIRONMENTAL SCIENCE & TECHNOLOGY （ 影响因子：9.028； 五年影响因子：9.922 ）

ISSN： 0013-936X

年卷期： 2018 年 52 卷 7 期

页码：

收录情况： SCI

摘要： It is hypothesized that polychlorinated diphenyl sulfides (PCDPSs) induce lethal toxicity in zebrafish which is mediated by aryl hydrocarbon receptor 2 (Ahr2) activation. In this study an assay was developed based on in vivo exposure of wild-type and Tg(cyp1a:gfp) transgenic zebrafish embryos/larvae to PCDPS congeners (i.e., six dichloro- to heptachlorodiphenyl sulfides) coupled with a zebrafish Ahr2-luciferase reporter gene (LRG) expression. Waterborne PCDPSs were found to be accumulated in zebrafish larvae, and exposure to PCDPSs led to a significant increase in mortality and cyp1s mRNA expression. Furthermore, treatment with PCDPSs caused a significant induction of Ahr2-LRG activity in COS-7 cells, and extremely significant correlations were observed between the in vivo median lethal concentrations and the levels of cyp1s mRNA expression and Ahr2 activation. Molecular dynamics simulations indicated the interaction between dioxins/dioxin-like compounds (DLCs) and six key amino acid residues in the ligand-binding domain of Ahr2 probably determined the susceptibility to dioxins/DLCs in zebrafish. These results strongly support the hypothesis that early life-stage mortality of zebrafish is initiated and mediated by Ahr2 activation.

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