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评估细胞荧光素酶报告基因检测中室内灰尘对人体核激素受体的干扰。

Assessing Indoor Dust Interference with Human Nuclear Hormone Receptors in Cell-Based Luciferase Reporter Assays.

机构信息

Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Department of Population Health Sciences, Harvard Graduate School of Arts and Sciences, Cambridge, Massachusetts, USA.

出版信息

Environ Health Perspect. 2021 Apr;129(4):47010. doi: 10.1289/EHP8054. Epub 2021 Apr 14.

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 () (100%; 46 of 46 samples), thyroid hormone receptor () (89%; 41 samples), and androgen receptor (AR) (87%; 40 samples); agonist activity on estrogen receptor () (96%; 44 samples); and binding competition with thyroxine () on serum transporter transthyretin (TTR) (98%; 45 samples). Effects were observed with as little as 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: , , ; , , ; , , ; , , ; unknown-potency: , , ; , , ), 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.

摘要

背景

全氟和多氟烷基物质(PFAS)、有机磷酸酯(OPE)和多溴二苯醚(PBDE)是从建筑材料迁移到空气和灰尘中的激素扰乱化学物质。

目的

我们旨在量化 46 个灰尘样本的激素活性,并确定驱动观察到的活性的化学物质。

方法

我们评估了基于 Tox21 高通量筛选数据的原始或效力加权浓度转换的 42 种测量的 PFAS、OPE 和 PBDE 灰尘浓度与五种基于细胞的荧光素酶报告基因测定中提取的灰尘的激素活性之间的关联。

结果

所有灰尘样本均具有激素活性,表现出对过氧化物酶体增殖物激活受体(PPAR)(100%;46 个样本中的 46 个)、甲状腺激素受体(TR)(89%;41 个样本)和雄激素受体(AR)(87%;40 个样本)的拮抗活性;对雌激素受体(ER)(96%;44 个样本)具有激动活性;并与血清转运蛋白转甲状腺素(TTR)上的甲状腺素(T4)结合竞争(98%;45 个样本)。仅提取 0.001 灰尘即可观察到效果。在每个化学类别回归模型中,效力加权或未知效力化学浓度的四分位距增加与灰尘提取物的激素活性升高相关(效力加权:PPARγ、PPARα、AR;TR、ERβ、ERα;GPER1、GPER2、GPER3;TTR、PPARγ、PPARα;未知效力:PPARγ、PPARα、AR;TR、ERβ、ERα),调整了具有活性、非活性和未知 Tox21 指定的化学物质。

讨论

所有室内灰尘样本均表现出激素活性,与 PFAS、PBDE 和 OPE 水平相关。基于细胞的报告基因检测是相对便宜的,是对建筑物居住者暴露于的化学混合物毒性负荷的健康相关评估。https://doi.org/10.1289/EHP8054.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/afc4/8045486/83e746154bdd/ehp8054_f1.jpg

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