Chlorpropham, a carbamate ester herbicide, has an endocrine-disrupting potential by inhibiting the homodimerization of human androgen receptor. (15th May 2023)

• Record Type: Journal Article
• Authors: Jeong, Da-Hyun; Jung, Da-Woon; Jang, Cheol-Ho; Kim, Uk-Jin; Park, Yooheon; Park, Yeonhwa; Lee, Hee-Seok
• Is Part Of: Environmental pollution. Volume 325(2023)
• Publication Date: 2023-05-15
• Subjects: Chlorpropham -- Endocrine-disrupting potential -- Androgen receptor -- Genomic pathway; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2023.121437
• Languages: English
• ISSNs: 0269-7491

Abstract

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. Graphical abstract: Image 1 Highlights: Chlorpropham could have endocrine disrupting effects. Chlorpropham was determined to be an AR antagonist in transcriptional activation assay. Chlorpropham suppressed the dimerization of AR in cytoplasm. This suppressing cause to block the translocation of cytoplasmic AR proteins to nucleus. AR antagonistic effect caused by suppressing the dimerization of ligand-bound ARs in cytoplasm.