In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components.
In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components.
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DOI：
10.1016/j.toxlet.2014.04.017
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发表时间：
2014-07-15
影响因子：
3.5
通讯作者：
Stapleton, Heather M.
中科院分区：
文献类型：
--
作者：
Belcher, Scott M.;Cookman, Clifford J.;Patisaul, Heather B.;Stapleton, Heather M.
关键词：
FireMaster®550(FM 550)是一种溴化阻燃剂和三芳基磷酸酯阻燃剂的混合物，用于聚氨酯泡沫塑料产品。主要成分还用于许多其他应用，因此是常见的家庭和工业污染物。我们之前的动物研究表明，FM550暴露可能会改变新陈代谢，导致体重增加。本研究采用人核受体(NR)荧光素酶报告基因分析方法，评价FM 550及其已知在建立或调节能量平衡中的成分在NRS的激动剂作用。FM550只有在脂肪细胞分化PPARγ的主调节子上才有明显的激动剂活性。因此，更详细地研究了FM550在PPARγ上的浓度响应关系和相对活性，定义了每个化学成分的贡献，并与典型的PPARγ环境配体三苯基锡和三丁基锡的活性进行了比较。结果表明，FM550的主要代谢干扰作用可能是由PPARγ上三芳基磷酸的活性介导的，并已确定TPP是一种候选的代谢干扰物，也起到细胞毒剂的作用。
Firemaster® 550 (FM 550) is a mixture of brominated and triarylphosphate flame retardants used in polyurethane foam-based products. The primary components are also used in numerous other applications and are thus common household and industrial contaminants. Our previous animal studies suggested that FM 550 exposure may alter metabolism and cause weight gain. Employing human nuclear receptor (NR) luciferase reporter assays, the goal of this study was to evaluate the agonist actions of FM 550 and its constituent compounds at NRs with known roles in establishing or regulating energy balance. FM 550 was found to have significant agonist activity only at the master regulator of adipocyte differentiation PPARγ. As a result, the concentration response relationships and relative activities of FM 550 at PPARγ were investigated in more detail with the contribution of each chemical component defined and compared to the activities of the prototypical PPARγ environmental ligands triphenyltin and tributylytin. The resulting data indicated that the primary metabolic disruptive effects of FM 550 were likely mediated by the activity of the triarylphosphates at PPARγ, and have identified TPP as a candidate metabolic disruptor that also acts as a cytotoxicant.
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