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Toxicol In Vitro. 2013 Sep;27(6):1634-43. doi: 10.1016/j.tiv.2013.04.005. Epub 2013 Apr 18.

Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation.

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Institute for Environmental Studies (IVM) and Amsterdam Global Change Institute, VU University, 1081 HV Amsterdam, The Netherlands.


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.


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

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