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氯苯胺灵,一种氨基甲酸酯类除草剂,通过抑制人类雄激素受体的同二聚化作用而具有内分泌干扰潜能。

Chlorpropham, a carbamate ester herbicide, has an endocrine-disrupting potential by inhibiting the homodimerization of human androgen receptor.

作者信息

Jeong Da-Hyun, Jung Da-Woon, Jang Cheol-Ho, Kim Uk-Jin, Park Yooheon, Park Yeonhwa, Lee Hee-Seok

机构信息

Department of Food Science and Biotechnology, Chung-Ang University, Anseong, 17546, Republic of Korea.

Department of Food Science and Biotechnology, Dongguk University, Goyang, 10326, Republic of Korea.

出版信息

Environ Pollut. 2023 May 15;325:121437. doi: 10.1016/j.envpol.2023.121437. Epub 2023 Mar 10.

DOI:10.1016/j.envpol.2023.121437
PMID:36907237
Abstract

This study was carried out to provide the evidence with respect to the adverse potential of chlorpropham, a representative carbamate ester herbicide product, on the endocrine system by using in vitro testing methods in accordance with the Organization for Economic Cooperation and Development Test Guideline No. 458 (22Rv1/MMTV_GR-KO human androgen receptor [AR] transcriptional activation assay) and a bioluminescence resonance energy transfer-based AR homodimerization assay. Results revealed that chlorpropham had no AR agonistic effects, but it was determined to be a true AR antagonist without intrinsic toxicity against the applied cell lines. In the mechanism of chlorpropham-induced AR-mediated adverse effects, chlorpropham suppressed cytoplasmic AR translocation to the nucleus by inhibiting the homodimerization of the activated ARs. This suggests that chlorpropham exposure caused endocrine-disrupting effects through its interactions with human AR. Additionally, this study might help identify the genomic pathway of the AR-mediated endocrine-disrupting potential of N-phenyl carbamate herbicides.

摘要

本研究旨在依据经济合作与发展组织测试指南第458号(22Rv1/MMTV_GR-KO人雄激素受体[AR]转录激活试验)以及基于生物发光共振能量转移的AR同源二聚化试验,采用体外测试方法,提供关于典型氨基甲酸酯类除草剂氯苯胺灵对内分泌系统潜在不良影响的证据。结果显示,氯苯胺灵无AR激动作用,但经测定它是一种真正的AR拮抗剂,对所应用的细胞系无内在毒性。在氯苯胺灵诱导的AR介导的不良反应机制中,氯苯胺灵通过抑制活化AR的同源二聚化来抑制细胞质AR向细胞核的转位。这表明氯苯胺灵暴露通过其与人AR的相互作用导致内分泌干扰效应。此外,本研究可能有助于确定N-苯基氨基甲酸酯类除草剂AR介导的内分泌干扰潜力的基因组途径。

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