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Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays
Environmental Health Perspectives ( IF 10.1 ) Pub Date : 2021-4-14 , DOI: 10.1289/ehp8054
Anna S Young 1, 2 , Thomas Zoeller 3 , Russ Hauser 1 , Tamarra James-Todd 1 , Brent A Coull 1 , Peter A Behnisch 4 , Abraham Brouwer 4 , Hongkai Zhu 5 , Kurunthachalam Kannan 5 , Joseph G Allen 1
Affiliation  

Abstract

Background:

Per- and polyfluoroalkyl substances (PFAS), organophosphate esters (OPEs), and polybrominated diphenyl ethers (PBDEs) are hormone-disrupting chemicals that migrate from building materials into air and dust.

Objectives:

We aimed to quantify the hormonal activities of 46 dust samples and identify chemicals driving the observed activities.

Methods:

We evaluated associations between hormonal activities of extracted dust in five cell-based luciferase reporter assays and dust concentrations of 42 measured PFAS, OPEs, and PBDEs, transformed as either raw or potency-weighted concentrations based on Tox21 high-throughput screening data.

Results:

All dust samples were hormonally active, showing antagonistic activity toward peroxisome proliferator-activated receptor (PPARγ2) (100%; 46 of 46 samples), thyroid hormone receptor (TRβ) (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor (ERα) (96%; 44 samples); and binding competition with thyroxine (T4) on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 4μg of extracted dust. In regression models for each chemical class, interquartile range increases in potency-weighted or unknown-potency chemical concentrations were associated with higher hormonal activities of dust extracts (potency-weighted: ΣPFASTRβ, 28%, p<0.05; ΣOPEsTRβ, 27%, p=0.08; ΣPBDEsTRβ, 20%, p<0.05; ΣPBDEsERα, 7.7%, p=0.08; unknown-potency: ΣOPEsTTR, 34%, p<0.05; ΣOPEsAR, 13%, p=0.06), adjusted for chemicals with active, inactive, and unknown Tox21 designations.

Discussion:

All indoor dust samples exhibited hormonal activities, which were associated with PFAS, PBDE, and OPE levels. Reporter gene cell-based assays are relatively inexpensive, health-relevant evaluations of toxic loads of chemical mixtures that building occupants are exposed to. https://doi.org/10.1289/EHP8054



中文翻译:

在基于细胞的荧光素酶报告基因检测中评估室内灰尘对人类核激素受体的干扰

摘要

背景:

全氟和多氟烷基物质 (PFAS)、有机磷酸酯 (OPE) 和多溴联苯醚 (PBDE) 是会干扰激素的化学物质,会从建筑材料迁移到空气和灰尘中。

目标:

我们旨在量化 46 个灰尘样本的荷尔蒙活动,并确定驱动观察到的活动的化学物质。

方法:

我们评估了五种基于细胞的荧光素酶报告分析中提取的粉尘的激素活性与 42 种测量的 PFAS、OPE 和 PBDE 的粉尘浓度之间的关联,根据 Tox21 高通量筛选数据转换为原始浓度或效能加权浓度。

结果:

所有灰尘样品均具有激素活性,对过氧化物酶体增殖物激活受体显示出拮抗活性(PPARγ2个)(100%;46 个样本中的 46 个),甲状腺激素受体(TRβ)(89%;41 个样本)和雄激素受体 (AR)(87%;40 个样本);对雌激素受体的激动剂活性(急诊室α) (96%; 44 个样本); 并与甲状腺素竞争结合(4个) 血清转运甲状腺素运载蛋白 (TTR)(98%;45 个样本)。观察到的影响少至4个μG提取的灰尘。在每个化学类别的回归模型中,效力加权或未知效力化学浓度的四分位间距增加与粉尘提取物的更高激素活性相关(效力加权:Σ全氟辛烷磺酸TRβ,28%,p<0.05;ΣOPEsTRβ,27%,p=0.08;Σ多溴二苯醚TRβ,20%,p<0.05;Σ多溴二苯醚急诊室α,7.7%,p=0.08; 未知效力:ΣOPEsTTR,34%,p<0.05;ΣOPEs增强现实,13%,p=0.06), 针对具有活性、非活性和未知 Tox21 名称的化学品进行了调整。

讨论:

所有室内灰尘样本都显示出与 PFAS、PBDE 和 OPE 水平相关的激素活性。基于报告基因细胞的检测是相对便宜的,对建筑物居住者接触的化学混合物的有毒负荷进行健康相关的评估。https://doi.org/10.1289/EHP8054

更新日期:2021-04-14
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