Abstract
Cell exposure to atmospheric polycyclic aromatic hydrocarbons (PAHs) is closely associated with DNA damage and genomic instability. We assessed the mechanisms of chronic and acute PAH exposure-induced genotoxicity in two human lung epithelial cell lines, A549 and NC-H1975. We sampled atmospheric PAHs at the Xixi Campus, Zhejiang University in Hangzhou, China during August (non-haze episode) and November (haze episode) 2015. We identified vehicle emissions as a dominant anthropogenic PAH source in our study. PAHs were extracted according to the United States Environmental Protection Agency Method TO-13A. We found that chronic PAH exposure saturated lung cell xenobiotic metabolic pathways, promoting intercellular reactive oxygen species production and accumulation. Chronic alteration of the cellular redox status resulted in DNA damage and genomic instability. Chronic PAH exposure also perturbed the cellular DNA damage response, inducing S phase arrest and inhibiting apoptosis. Dysregulation of PAH metabolism and the DNA damage response altered cellular homeostasis and increased cell susceptibility to subsequent PAH exposures, thereby enhancing the likelihood of genomic mutation and instability.
Highlights
Atmospheric particulate matter (PM) pollution is a growing concern worldwide due to its negative effects on air quality, climate change, and human health [1,2,3,4,5,6]
The metabolic activation of polycyclic aromatic hydrocarbons (PAHs) via xenobiotic-metabolizing enzymes (XMEs) leads to carcinogenicity [34]
PAH-diol-epoxides react with DNA to produce adducts that have been identified in lung tissues, and might cause genomic instability and mutation [35]
Summary
Atmospheric particulate matter (PM) pollution is a growing concern worldwide due to its negative effects on air quality, climate change, and human health [1,2,3,4,5,6]. Atmospheric polycyclic aromatic hydrocarbons (PAHs) are considered priority environmental pollutants due to their carcinogenicity and mutagenicity [7,8,9]. Procarcinogens, including PAHs, do not directly induce genotoxicity [10]. PAH activation involves the formation of phenols, catechols, quinones, diol-epoxides, o-quinones, and radical cations [11,12,13], which can react with DNA to form DNA adducts, leading to deletions, fusions, translocations, or aneuploidy. The carcinogenic PAHs can induce DNA damage in various human cell lines [16, 17], activating DDR pathways regulated by P53 and its downstream gene products to regulate and maintain genomic stability [18,19,20]
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