PMID- 27208783 OWN - NLM STAT- MEDLINE DCOM- 20180122 LR - 20190318 IS - 1873-6750 (Electronic) IS - 0160-4120 (Linking) VI - 94 DP - 2016 Sep TI - Assessment of the endocrine-disrupting effects of short-chain chlorinated paraffins in in vitro models. PG - 43-50 LID - S0160-4120(16)30180-5 [pii] LID - 10.1016/j.envint.2016.05.007 [doi] AB - Short-chain chlorinated paraffins (SCCPs), which are candidate persistent organic pollutants (POPs) according to the Stockholm Convention, are of great concern because of their persistent bioaccumulation, long-range transport and potential adverse health effects. However, data on the endocrine-disrupting effects of SCCPs remain scarce. In this study, we first adopted two in vitro models (reporter gene assays and H295R cell line) to investigate the endocrine-disrupting effects of three SCCPs (C10-40.40%, C10-66.10% and C11-43.20%) via receptor mediated and non-receptor mediated pathway. The dual-luciferase reporter gene assay revealed that all test chemicals significantly induced estrogenic effects, which were mediated by estrogen receptor alpha (ERalpha), in the following order: C11-43.20%>C10-66.10%>C10-40.40%. Notably, C10-40.40% and C10-66.10% also demonstrated remarkable anti-estrogenic activities. Only C11-43.20% showed glucocorticoid receptor-mediated (GR) antagonistic activity, with a RIC20 value of 2.6x10(-8)mol/L. None of the SCCPs showed any agonistic or antagonistic activities against thyroid receptor beta (TRbeta). Meanwhile, all test SCCPs stimulated the secretion of 17beta-estradiol (E2). Both C10-66.10% and C11-43.20% increased the production of cortisol at a high level in H295R cell lines. In order to explore the possible mechanism underlying the endocrine-disrupting effects of SCCPs through the non-receptor pathway, the mRNA levels of 9 steroidogenic genes were measured by real-time polymerase chain reaction (RT-PCR). StAR, 17betaHSD, CYP11A1, CYP11B1, CYP19 and CYP21 were upregulated in a concentration-dependent manner by all chemicals. The data provided here emphasized that comprehensive assessments of the health and ecological risks of emerging contaminants, such as SCCPs, are of great concern and should be investigated further. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Zhang, Quan AU - Zhang Q AD - College of Environment, Zhejiang University of Technology, Hangzhou 310032, China; College of Environment & Resource Sciences, Zhejiang University, Hangzhou 310058, China. FAU - Wang, Jinghua AU - Wang J AD - College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. FAU - Zhu, Jianqiang AU - Zhu J AD - College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. FAU - Liu, Jing AU - Liu J AD - College of Environment & Resource Sciences, Zhejiang University, Hangzhou 310058, China. FAU - Zhang, Jianyun AU - Zhang J AD - College of Environment & Resource Sciences, Zhejiang University, Hangzhou 310058, China. FAU - Zhao, Meirong AU - Zhao M AD - College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: zhaomr@zjut.edu.cn. LA - eng PT - Journal Article DEP - 20160518 PL - Netherlands TA - Environ Int JT - Environment international JID - 7807270 RN - 0 (Endocrine Disruptors) RN - 0 (Environmental Pollutants) RN - 0 (Estrogen Receptor alpha) RN - 0 (Hydrocarbons, Chlorinated) RN - 0 (Phosphoproteins) RN - 0 (Receptors, Glucocorticoid) RN - 0 (Thyroid Hormone Receptors beta) RN - 0 (steroidogenic acute regulatory protein) RN - 4TI98Z838E (Estradiol) RN - 8002-74-2 (Paraffin) RN - 9035-51-2 (Cytochrome P-450 Enzyme System) RN - EC 1.1.- (17-Hydroxysteroid Dehydrogenases) RN - EC 1.1.1.51 (3 (or 17)-beta-hydroxysteroid dehydrogenase) SB - IM MH - 17-Hydroxysteroid Dehydrogenases/genetics MH - Animals MH - CHO Cells MH - Cell Line, Tumor MH - Cricetulus MH - Cytochrome P-450 Enzyme System/genetics MH - Endocrine Disruptors/*toxicity MH - Environmental Pollutants/*toxicity MH - Estradiol/metabolism MH - Estrogen Receptor alpha/genetics/metabolism MH - Genes, Reporter MH - Humans MH - Hydrocarbons, Chlorinated/*toxicity MH - Paraffin/*toxicity MH - Phosphoproteins/genetics MH - Receptors, Glucocorticoid/antagonists & inhibitors MH - Thyroid Hormone Receptors beta/genetics OTO - NOTNLM OT - *Endocrine-disrupting effects OT - *Estrogen receptor alpha OT - *Glucocorticoid receptor OT - *H295R cell line OT - *Short-chain chlorinated paraffins OT - *Thyroid receptor beta EDAT- 2016/05/22 06:00 MHDA- 2018/01/23 06:00 CRDT- 2016/05/22 06:00 PHST- 2016/02/29 00:00 [received] PHST- 2016/04/18 00:00 [revised] PHST- 2016/05/07 00:00 [accepted] PHST- 2016/05/22 06:00 [entrez] PHST- 2016/05/22 06:00 [pubmed] PHST- 2018/01/23 06:00 [medline] AID - S0160-4120(16)30180-5 [pii] AID - 10.1016/j.envint.2016.05.007 [doi] PST - ppublish SO - Environ Int. 2016 Sep;94:43-50. doi: 10.1016/j.envint.2016.05.007. Epub 2016 May 18.