title: Steroid hormone related effects of marine persistent organic pollutants in human H295R adrenocortical carcinoma cells.
abstract: Persistent organic pollutants (POPs) such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorobiphenyl (PCB) 126 and 153, perfluorooctanesulfonic acid (PFOS), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), tributyltin (TBT), and methylmercury (MeHg) can be accumulated in seafood and then form a main source for human exposure. Some POPs have been associated with changes in steroid hormone levels in both humans and animals. This study describes the in vitro effects of these POPs and mixtures thereof in H295R adrenocortical carcinoma cells. Relative responses for 13 steroid hormones and 7 genes involved in the steroidogenic pathway, and CYP1A1, were analyzed. PFOS induced the most pronounced effects on steroid hormone levels by significantly affecting 9 out of 13 hormone levels measured, with the largest increases found for 17β-estradiol, corticosterone, and cortisol. Furthermore, TCDD, both PCBs, and TBT significantly altered steroidogenesis. Increased steroid hormone levels were accompanied by related increased gene expression levels. The differently expressed genes were MC2R, CYP11B1, CYP11B2, and CYP19A1 and changes in gene expression levels were more sensitive than changes in hormone levels. The POP mixtures tested showed mostly additive effects, especially for DHEA and 17β-estradiol levels. This study shows that some seafood POPs are capable of altering steroidogenesis in H295R cells at concentrations that mixtures might reach in human blood, suggesting that adverse health effects cannot be excluded.
authors.affiliation: Sub-department of Environmental Technology, Wageningen University, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands; Division of Human Nutrition, Wageningen University, Bomenweg 4, 6703 HD Wageningen, The Netherlands. Electronic address: myrthe.vandendungen@wur.nl.
authors.forename: Myrthe W
authors.initials: MW
authors.lastname: van den Dungen
authors.affiliation: RIKILT - Institute of Food Safety, Wageningen UR, Akkermaalsbos 2, 6708 WB Wageningen, The Netherlands. Electronic address: rijk.jeroen@gmail.com.
authors.forename: Jeroen C W
authors.initials: JC
authors.lastname: Rijk
authors.affiliation: Division of Human Nutrition, Wageningen University, Bomenweg 4, 6703 HD Wageningen, The Netherlands. Electronic address: ellen.kampman@wur.nl.
authors.forename: Ellen
authors.initials: E
authors.lastname: Kampman
authors.affiliation: Division of Human Nutrition, Wageningen University, Bomenweg 4, 6703 HD Wageningen, The Netherlands. Electronic address: wilma.steegenga@wur.nl.
authors.forename: Wilma T
authors.initials: WT
authors.lastname: Steegenga
authors.affiliation: Sub-department of Environmental Technology, Wageningen University, Bornse Weilanden 9, 6708 WG Wageningen, The Netherlands. Electronic address: tinka.murk@wur.nl.
authors.forename: Albertinka J
authors.initials: AJ
authors.lastname: Murk
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary / Q000096:biosynthesis; D052244:Endocrine Disruptors / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D013256:Steroids / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D018076:DNA, Complementary; D052244:Endocrine Disruptors; D006728:Hormones; D013256:Steroids; D014874:Water Pollutants, Chemical; D012313:RNA
keywords: Adrenal cortex cell line; Endocrine disruption; Gene expression; H295R; Persistent organic pollutants (POPs); Steroid hormones