title: Assessment of the endocrine-disrupting effects of short-chain chlorinated paraffins in in vitro models.
abstract: 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 α (ERα), 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 2.6×10(-8)mol/L. None of the SCCPs showed any agonistic or antagonistic activities against thyroid receptor β (TRβ). Meanwhile, all test SCCPs stimulated the secretion of 17β-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, 17βHSD, 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.
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China; College of Environment & Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Jinghua
authors.initials: J
authors.lastname: Wang
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: College of Environment & Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: College of Environment & Resource Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Environment, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: zhaomr@zjut.edu.cn.
authors.forename: Meirong
authors.initials: M
authors.lastname: Zhao
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000818:Animals; D016466:CHO Cells; D045744:Cell Line, Tumor; D003412:Cricetulus; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity*; D010232:Paraffin / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D037042:Thyroid Hormone Receptors beta / Q000235:genetics; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D047628:Estrogen Receptor alpha; D006843:Hydrocarbons, Chlorinated; D010750:Phosphoproteins; D011965:Receptors, Glucocorticoid; D037042:Thyroid Hormone Receptors beta; D000098682:Steroidogenic Acute Regulatory Protein; D004958:Estradiol; D010232:Paraffin; D003577:Cytochrome P-450 Enzyme System; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase
keywords: Endocrine-disrupting effects; Estrogen receptor α; Glucocorticoid receptor; H295R cell line; Short-chain chlorinated paraffins; Thyroid receptor β