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鉴定德克萨斯州休斯顿大气化学混合物与肺细胞中癌症和炎症相关基因的转录反应。

Identifying the Transcriptional Response of Cancer and Inflammation-Related Genes in Lung Cells in Relation to Ambient Air Chemical Mixtures in Houston, Texas.

机构信息

Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

Curriculum in Toxicology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States.

出版信息

Environ Sci Technol. 2020 Nov 3;54(21):13807-13816. doi: 10.1021/acs.est.0c02250. Epub 2020 Oct 16.

Abstract

Atmospheric pollution represents a complex mixture of air chemicals that continually interact and transform, making it difficult to accurately evaluate associated toxicity responses representative of real-world exposure. This study leveraged data from a previously published article and reevaluated lung cell transcriptional response induced by outdoor atmospheric pollution mixtures using field-based exposure conditions in the industrialized Houston Ship Channel. The tested hypothesis was that individual and co-occurring chemicals in the atmosphere relate to altered expression of critical genes involved in inflammation and cancer-related processes in lung cells. Human lung cells were exposed at an air-liquid interface to ambient air mixtures for 4 h, with experiments replicated across 5 days. Real-time monitoring of primary and secondary gas-phase pollutants, as well as other atmospheric conditions, was simultaneously conducted. Transcriptional analysis of exposed cells identified critical genes showing differential expression associated with both individual and chemical mixtures. The individual pollutant identified with the largest amount of associated transcriptional response was benzene. Tumor necrosis factor () and interferon regulatory factor 1 () were identified as key upstream transcription factor regulators of the cellular response to benzene. This study is among the first to measure lung cell transcriptional responses in relation to real-world, gas-phase air mixtures.

摘要

大气污染是一种复杂的空气化学混合物,不断相互作用和转化,使得准确评估与实际暴露相关的毒性反应变得困难。本研究利用先前发表的一篇文章中的数据,并在工业化的休斯顿船运航道的现场暴露条件下,重新评估了户外大气污染混合物对肺细胞转录反应的影响。研究假设是,大气中的单个和共存化学物质与参与炎症和癌症相关过程的关键基因的表达改变有关。人类肺细胞在气-液界面上暴露于环境空气混合物中 4 小时,实验在 5 天内重复进行。同时实时监测主要和次要气相污染物以及其他大气条件。暴露细胞的转录分析确定了与个体和化学混合物都相关的差异表达的关键基因。与最大量相关转录反应的单个污染物是苯。肿瘤坏死因子(TNF)和干扰素调节因子 1(IRF1)被确定为苯引起的细胞反应的关键上游转录因子调节剂。这项研究是首次测量与实际气相空气混合物相关的肺细胞转录反应的研究之一。

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