Characterization of adipogenic, PPARγ, and TRβ activities in house dust extracts and their associations with organic contaminants.
Characterization of adipogenic, PPARγ, and TRβ activities in house dust extracts and their associations with organic contaminants.
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室内灰尘提取物中脂肪生成、PPARγ和TRβ活性的表征及其与有机污染物的关系
DOI：
10.1016/j.scitotenv.2020.143707
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Stapleton HM
中科院分区：
文献类型：
--
作者：
Kassotis CD;Hoffman K;Phillips AL;Zhang S;Cooper EM;Webster TF;Stapleton HM
在这项研究中，我们试图扩大我们之前关于粉尘中的生物活性与相关的有机污染物之间的联系的研究。从北卡罗来纳州中心家庭(n=188)采集粉尘样本，提取溶剂，并将其分成两部分，一部分用于三种不同的生物分析(核受体激活/抑制和脂肪细胞发育)，另一部分用于质谱分析(对124种有机污染物进行有针对性的测量，包括阻燃剂、多氯联苯、全氟烷基物质、杀虫剂、邻苯二甲酸酯和多环芳烃)。大约80%的粉尘提取物通过甘油三酯积累(65%)和/或脂肪细胞增殖前期(50%)，在与儿童和成人估计暴露的浓度(例如~20μg/孔粉尘)相当的浓度下显示出显著的成脂活性。约76%的样本拮抗甲状腺受体β，21%的样本激活过氧化物酶体增殖物激活受体γ。甘油三酯的积累与tr-β拮抗作用显著相关。在至少75%的样本中检测到65种污染物；其中26种与成脂活性有关，10种与trβ拮抗有关。回归模型被用来评估单个污染物与成脂和trβ生物活性的相关性，并且许多单个污染物显著相关。探索性的g-计算模型被用来评估混合物的效果。污染物混合物与甘油三酯的积累呈正相关，而且影响的幅度大于任何单独测量的化学物质。混合物暴露每增加四分位数，甘油三酯累积增加212%(RR=3.12，95%可信区间：1.58，6.17)。这些结果表明，房屋灰尘中存在的复杂化学混合物在环境浓度下可能会在体外诱导成脂活性，值得进一步研究。
In this study, we sought to expand our previous research on associations between bioactivities in dust and associated organic contaminants. Dust samples were collected from central NC homes (n=188), solvent extracted, and split into two fractions, one for analysis using three different bioassays (nuclear receptor activation/inhibition and adipocyte development) and one for mass spectrometry (targeted measurement of 124 organic contaminants, including flame retardants, polychlorinated biphenyls, perfluoroalkyl substances, pesticides, phthalates, and polycyclic aromatic hydrocarbons). Approximately 80% of dust extracts exhibited significant adipogenic activity at concentrations that are comparable to estimated exposure for children and adults (e.g. ~20 μg/well dust) via either triglyceride accumulation (65%) and/or pre-adipocyte proliferation (50%). Approximately 76% of samples antagonized thyroid receptor beta (TRβ), and 21% activated peroxisome proliferator activated receptor gamma (PPARγ). Triglyceride accumulation was significantly correlated with TRβ antagonism. Sixty-five contaminants were detected in at least 75% of samples; of these, 26 were correlated with adipogenic activity and ten with TRβ antagonism. Regression models were used to evaluate associations of individual contaminants with adipogenic and TRβ bioactivities, and many individual contaminants were significantly associated. An exploratory g-computation model was used to evaluate the effect of mixtures. Contaminant mixtures were positively associated with triglyceride accumulation, and the magnitude of effect was larger than for any individually measured chemical. For each quartile increase in mixture exposure, triglyceride accumulation increased by 212% (RR=3.12 and 95% confidence interval: 1.58, 6.17). These results suggest that complex mixtures of chemicals present in house dust may induce adipogenic activity in vitro at environmental concentrations and warrants further research.
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影响因子：
11.4
作者：
Fang M;Webster TF;Stapleton HM
通讯作者：
Stapleton HM
影响因子：
--
作者：
Fan, Xinghua;Kubwabo, Cariton;Jones-Otazo, Heather
通讯作者：
Jones-Otazo, Heather
影响因子：
11.8
作者：
Hoffman, Kate;Lorenzo, Amelia;Sosa, Julie Ann
通讯作者：
Sosa, Julie Ann
影响因子：
11.8
作者：
Hammel SC;Levasseur JL;Hoffman K;Phillips AL;Lorenzo AM;Calafat AM;Webster TF;Stapleton HM
通讯作者：
Stapleton HM
DOI：
10.1038/sj.jea.7500307
发表时间：
2004-01-01
期刊：
JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY
影响因子：
--
作者：
Colt, JS;Lubin, J;Hartge, P
通讯作者：
Hartge, P