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室内灰尘中分离出的化学混合物会破坏甲状腺受体β信号。

Chemical Mixtures Isolated from House Dust Disrupt Thyroid Receptor β Signaling.

机构信息

Nicholas School of the Environment , Duke University , Box 90328, Durham , North Carolina 27708 , United States.

Department of Surgery , University of California at San Francisco , 513 Parnassus Avenue , San Francisco , California 94117 , United States.

出版信息

Environ Sci Technol. 2018 Oct 16;52(20):11857-11864. doi: 10.1021/acs.est.8b03283. Epub 2018 Sep 25.

Abstract

House dust is a source of exposure to chemicals that can impact hormone regulation. This study was designed to evaluate the potential of house dust mixtures ( n = 137) to disrupt thyroid hormone nuclear receptor signaling in a cell-based reporter assay and to examine associations with thyroid hormones (TH) measured in residents of the homes. Approximately 41% of the extracts (ranging from 10.5 to 4.097 μg of dust/mL) significantly antagonized thyroid receptor β (TRβ) signaling by 20-67% relative to the hormone control. The concentrations of 12 flame retardants (FRs) quantified in the mixtures were significantly correlated with TRβ antagonism; however, they were inactive when tested individually. We hypothesize that the observed antagonism is due to mixture effects or unidentified compounds that co-occur with FRs. Dust extract potency was significantly associated with free thyroxine (FT4, r = -0.64, p < 0.001), suggesting that more potent dust samples are associated with higher FT4 levels in residents. Overall, these results suggest that house dust is a significant source of exposure to TH-disrupting chemicals, and TRβ may have a role in mediating effects of exposure on TH levels. Additional studies are needed to identify the chemical(s) driving the observed effects on TRβ and to determine if these changes lead to any adverse outcomes.

摘要

室内灰尘是暴露于可影响激素调节的化学物质的来源。本研究旨在评估室内灰尘混合物(n=137)在基于细胞的报告基因检测中干扰甲状腺激素核受体信号的潜力,并研究其与居住在这些住宅中的居民体内甲状腺激素(TH)之间的关联。约 41%的提取物(范围为 10.5 至 4.097μg 灰尘/mL)相对于激素对照,对甲状腺受体β(TRβ)信号的拮抗作用达到 20-67%。混合物中定量的 12 种阻燃剂(FRs)与 TRβ 拮抗作用显著相关;然而,当单独测试时,它们没有活性。我们假设观察到的拮抗作用是由于混合物效应或与 FRs 共同存在的未识别化合物所致。灰尘提取物的效力与游离甲状腺素(FT4)显著相关(r=-0.64,p<0.001),表明效力更高的灰尘样本与居民体内更高的 FT4 水平相关。总的来说,这些结果表明,室内灰尘是接触干扰甲状腺激素的化学物质的重要来源,TRβ 可能在介导暴露对 TH 水平的影响方面发挥作用。需要进一步的研究来确定驱动 TRβ 观察到的效应的化学物质,并确定这些变化是否会导致任何不良后果。

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