PMID- 30609499 OWN - NLM STAT- MEDLINE DCOM- 20190221 LR - 20210816 IS - 1879-1298 (Electronic) IS - 0045-6535 (Linking) VI - 218 DP - 2019 Mar TI - The endocrine-disrupting potential of four chlorophenols by in vitro and in silico assay. PG - 941-947 LID - S0045-6535(18)32306-3 [pii] LID - 10.1016/j.chemosphere.2018.11.199 [doi] AB - Chlorophenols (CPs) have mainly been used as a biocide, wood treatment agent and a byproduct of bleaching in paper mills. They have been a topic of concern due to their wide spread and potential effects on human and wildlife. However, data on the thresholds and effects of the number of chlorine atoms on the endocrine-disrupting potential of CPs remain scarce. In this study, we adopted two in vitro models (reporter gene assays and H295R cell line) to investigate the endocrine-disrupting effects of four CPs (pentachlorophenol (PCP), 2,4,6-trichlorophenol (2,4,6-TCP), 2,4-dichlorophenol (2,4-DCP) and 2-chlorophenol (2-CP)). The molecular docking platform was adopted to further confirm the results of the in vitro assessment. Our results revealed that PCP exhibited oestrogen receptor alpha (ERalpha) agonistic activity at the concentration of 10(-5) M and the value of REC(20) was 1.9 x 10(-6) M. PCP and 2, 4, 6-TCP showed anti-oestrogenic activities with a RIC(20) value of 2.8 x 10(-7)and 2.9 x 10(-6) M, respectively. Notably, only PCP exhibited thyroid hormone receptor beta (TRbeta) antagonistic activity occurred at the concentration of 10(-5) M, with a RIC(20) value of 1.3 x 10(-6) M. The oestrogenic and thyroid hormone effects of CPs may be dependent on the number of chlorine atoms. A higher number of chlorine atoms indicated the higher effect of four CPs. The results of molecular docking were consistent with the reporter gene assay. For H295R cell line assay, PCP induced the StAR upregulation, while CYP17 was downregulated in a concentration-dependent manner by PCP and 2, 4, 6-TCP. CI - Copyright (c) 2018 Elsevier Ltd. All rights reserved. FAU - Yu, Chang AU - Yu C AD - Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China. FAU - Wang, Chi AU - Wang C AD - Longyou Huashui Drinking Water Industry Company, Quzhou, Zhejiang, 324400, China. FAU - Lu, Zhengbiao AU - Lu Z AD - Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China. FAU - Zhang, Chen AU - Zhang C AD - School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, Guangdong, 510006, China. FAU - Dai, Wei AU - Dai W AD - Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China. FAU - Yu, Shuqing AU - Yu S AD - Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China. FAU - Lin, Shu AU - Lin S AD - Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China. FAU - Zhang, Quan AU - Zhang Q AD - Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou, Zhejiang, 310032, China. Electronic address: quanzhang@zjut.edu.cn. LA - eng PT - Journal Article DEP - 20181129 PL - England TA - Chemosphere JT - Chemosphere JID - 0320657 RN - 0 (Chlorophenols) RN - 0 (ESR1 protein, human) RN - 0 (Endocrine Disruptors) RN - 0 (Estrogen Receptor alpha) RN - 0 (Thyroid Hormone Receptors beta) SB - IM MH - Cell Line MH - Chlorophenols/*pharmacology MH - Endocrine Disruptors/*pharmacology MH - Endocrine System MH - Estrogen Receptor alpha/agonists MH - Humans MH - Molecular Docking Simulation MH - Thyroid Hormone Receptors beta/antagonists & inhibitors OTO - NOTNLM OT - Chlorophenols OT - Endocrine-disrupting effects OT - H295R OT - Molecular docking EDAT- 2019/01/06 06:00 MHDA- 2019/02/23 06:00 CRDT- 2019/01/06 06:00 PHST- 2018/10/08 00:00 [received] PHST- 2018/11/27 00:00 [revised] PHST- 2018/11/28 00:00 [accepted] PHST- 2019/01/06 06:00 [entrez] PHST- 2019/01/06 06:00 [pubmed] PHST- 2019/02/23 06:00 [medline] AID - S0045-6535(18)32306-3 [pii] AID - 10.1016/j.chemosphere.2018.11.199 [doi] PST - ppublish SO - Chemosphere. 2019 Mar;218:941-947. doi: 10.1016/j.chemosphere.2018.11.199. Epub 2018 Nov 29.