title: Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation.
abstract: Recent studies suggest that endocrine disrupting chemicals (EDCs) may form a risk factor for obesity by altering energy metabolism through epigenetic gene regulation. The goal of this study is to investigate the effects of a range of EDCs with putative obesogenic properties on global DNA methylation and adipocyte differentiation in vitro. Murine N2A and human SK-N-AS neuroblastoma cells and murine preadipocyte fibroblasts (3T3-L1) were exposed to tributyltin (TBT), diethylstilbestrol (DES), bisphenol A (BPA), 2,3,7,8-tetrachlorodibenzo-[p]-dioxin (TCDD), 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153), hexachlorobenzene (HCB), hexabromocyclododecane (HBCD), 2,2',4,4'-tetrabrominated diphenyl ether (BDE-47) , perfluorinated octyl acid (PFOA) and perfluorinated octyl sulfonate (PFOS). A modest decrease in global DNA methylation was observed in N2A cells exposed to 10 μM DES, BPA, TCDD, BDE-47, PCB-153 and 1 μM HCB, but no changes were found in the human SK-N-AS cells. We reveal for the first time that BDE-47 increases adipocyte differentiation in a dose-dependent manner (2.5-25 μM). Adipocyte differentiation was also enhanced by TBT (≥ 10 nM) and BPA (>10 μM) and inhibited by TCDD (≥ 0.1 nM). The other chemicals showed either modest or no effects on adipocyte differentiation at the concentrations tested (PFOA, PFOS and HBCD at 10 μM; PCB-153, 3.4 μM and HCB, 1 μM). This study demonstrates that selected EDCs can induce functional changes in murine adipocyte differentiation in vitro which are accompanied by decreased global DNA methylation.
authors.affiliation: Institute for Environmental Studies (IVM) and Amsterdam Global Change Institute, VU University, 1081 HV Amsterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Bastos Sales
authors.forename: J H
authors.initials: JH
authors.lastname: Kamstra
authors.forename: P H
authors.initials: PH
authors.lastname: Cenijn
authors.forename: L S
authors.initials: LS
authors.lastname: van Rijt
authors.forename: T
authors.initials: T
authors.lastname: Hamers
authors.forename: J
authors.initials: J
authors.lastname: Legler
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects*; D017738:Alkanesulfonic Acids / Q000633:toxicity; D000818:Animals; D001559:Benzhydryl Compounds / Q000633:toxicity; D002210:Caprylates / Q000633:toxicity; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects*; D004054:Diethylstilbestrol / Q000633:toxicity; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity; D005466:Fluorocarbons / Q000633:toxicity; D055768:Halogenated Diphenyl Ethers / Q000633:toxicity; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity; D006843:Hydrocarbons, Chlorinated / Q000633:toxicity; D051379:Mice; D010636:Phenols / Q000633:toxicity; D014220:Trialkyltin Compounds / Q000633:toxicity; D000098826:Bisphenol A Compounds
chemical_list: D017738:Alkanesulfonic Acids; D001559:Benzhydryl Compounds; D002210:Caprylates; D004054:Diethylstilbestrol; D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D005466:Fluorocarbons; D055768:Halogenated Diphenyl Ethers; D006842:Hydrocarbons, Brominated; D006843:Hydrocarbons, Chlorinated; D010636:Phenols; D014220:Trialkyltin Compounds; C511295:2,2',4,4'-tetrabromodiphenyl ether; C011559:tributyltin; C089796:hexabromocyclododecane; C023036:perfluorooctanoic acid; C076994:perfluorooctane sulfonic acid; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: 2,2′,4,4′,5,5′-hexachlorobiphenyl; 2,2′,4,4′-tetrabrominated diphenyl ether; 2,3,7,8-tetrachlorodibenzo-[p]-dioxin; Adipocyte differentiation; BDE-47; BPA; Bromodiphenylether; DES; EDCs; Endocrine disrupting chemicals; Epigenetics; HBCD; HCB; In vitro; Obesity; PCB-153; PFOA; PFOS; TBT; TCDD; Tributyltin; bisphenol A; diethylstilbestrol; endocrine disrupting chemicals; hexabromocyclododecane; hexachlorobenzene; perfluorinated octyl acid; perfluorinated octyl sulfonate; tributyltin