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: L Bastos Sales, J H Kamstra, P H Cenijn, L S van Rijt, T Hamers, J Legler
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 27 Issue 6 Pg. 1634-43 (Sep 2013) ISSN: 1879-3177 [Electronic] England
• PMID: 23603478 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Alkanesulfonic Acids
• Benzhydryl Compounds
• Caprylates
• Endocrine Disruptors
• Environmental Pollutants
• Fluorocarbons
• Halogenated Diphenyl Ethers
• Hydrocarbons, Brominated
• Hydrocarbons, Chlorinated
• Phenols
• Trialkyltin Compounds
• 2,2',4,4'-tetrabromodiphenyl ether
• tributyltin
• hexabromocyclododecane
• Diethylstilbestrol
• perfluorooctanoic acid
• perfluorooctane sulfonic acid
• bisphenol A

Topics

• 3T3-L1 Cells
• Adipocytes (cytology, drug effects)
• Alkanesulfonic Acids (toxicity)
• Animals
• Benzhydryl Compounds (toxicity)
• Caprylates (toxicity)
• Cell Differentiation (drug effects)
• Cell Line, Tumor
• DNA Methylation (drug effects)
• Diethylstilbestrol (toxicity)
• Endocrine Disruptors (toxicity)
• Environmental Pollutants (toxicity)
• Fluorocarbons (toxicity)
• Halogenated Diphenyl Ethers (toxicity)
• Humans
• Hydrocarbons, Brominated (toxicity)
• Hydrocarbons, Chlorinated (toxicity)
• Mice
• Phenols (toxicity)
• Trialkyltin Compounds (toxicity)