Adipogenic effects of a combination of the endocrine-disrupting compounds bisphenol A, diethylhexylphthalate, and tributyltin.

Adipogenic effects of a combination of the endocrine-disrupting compounds bisphenol A, diethylhexylphthalate, and tributyltin.
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DOI:
10.1159/000358913
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发表时间:
2014
期刊:
影响因子:
3.6
通讯作者:
Navarrete Santos A
Navarrete Santos A
中科院分区:
医学3区
文献类型:
--
作者:
Biemann R;Fischer B;Navarrete Santos A

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食品污染物双酚A(BPA)、邻苯二甲酸二辛酯(DEHP)和三丁基锡(TBT)是已知干扰脂肪生成的强效内分泌干扰化合物(EDC)。EDC通常以混合物而不是单一化合物的形式起作用。本研究的目的是研究同时暴露于BPA、DEHP和TBT对间充质干细胞分化为脂肪细胞的影响。将多能鼠间充质干细胞(C3 H10 T1/2)暴露于高浓度EDC混合物,即MIX高浓度(10 µmol/l BPA、100 µmol/l DEHP、100 nmol/l TBT)和环境相关浓度,即MIX低浓度(10 nmol/l BPA、100 nmol/l DEHP、1 nmol/l TBT)。在整个培养时间(0-12天)或在脂肪形成分化的不同阶段进行暴露。在细胞培养的第12天,分析脂肪细胞的量、甘油三酯含量(TG)和脂肪形成标记基因表达。MIX-高增加了脂肪细胞的发育和成脂标志物基因的表达,与暴露窗口无关。TG总量未增加。低浓度EDC混合物对脂肪形成没有明显影响。在EDC混合物中,TBT和DEHP的成脂作用优于BPA的单一作用。EDC的混合效应不能从单一化合物的实验中推断出来。
The food contaminants bisphenol A (BPA), diethylhexylphthalate (DEHP), and tributyltin (TBT) are potent endocrine-disrupting compounds (EDC) known to interfere with adipogenesis. EDC usually act in mixtures and not as single compounds. The aim of this study was to investigate the effects of a simultaneous exposure of BPA, DEHP, and TBT on mesenchymal stem cell differentiation into adipocytes. Multipotent murine mesenchymal stem cells (C3H10T1/2) were exposed to EDC mixtures in high concentrations, i.e. MIX-high (10 µmol/l BPA, 100 µmol/l DEHP, 100 nmol/l TBT), and in environmentally relevant concentrations, i.e. MIX-low (10 nmol/l BPA, 100 nmol/l DEHP, 1 nmol/l TBT). The exposure was performed either for the entire culture time (0-12 days) or at distinct stages of adipogenic differentiation. At day 12 of cell culture, the amount of adipocytes, triglyceride content (TG), and adipogenic marker gene expression were analyzed. MIX-high increased the development of adipocytes and the expression of adipogenic marker genes independently of the exposure window. The total TG amount was not increased. The low-concentrated EDC mixture had no obvious impact on adipogenesis. In EDC mixtures, the adipogenic effect of TBT and DEHP predominates single effects of BPA. Mixture effects of EDC are not deducible from single compound experiments.
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