TY - JOUR
T1 - Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentation
AU - Bastos Sales, L.
AU - Kamstra, J.H.
AU - Cenijn, P.H.
AU - van Rijt, L.S.
AU - Hamers, T.
AU - Legler, J.
PY - 2013
Y1 - 2013
N2 - 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. © 2013 Elsevier Ltd.
AB - 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. © 2013 Elsevier Ltd.
U2 - 10.1016/j.tiv.2013.04.005
DO - 10.1016/j.tiv.2013.04.005
M3 - Article
SN - 0887-2333
VL - 27
SP - 1634
EP - 1643
JO - Toxicology in Vitro
JF - Toxicology in Vitro
IS - 6
ER -