Bai Hongzhen, Wu Min, Zhang Hongjian, Tang Guping
State Key Laboratory of Industrial Control Technology, College of Control Science and Engineering, Zhejiang University, Hangzhou 310028, China.
Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
Oncotarget. 2017 Sep 15;8(45):79034-79045. doi: 10.18632/oncotarget.20891. eCollection 2017 Oct 3.
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.
细胞暴露于大气多环芳烃（PAHs）与DNA损伤和基因组不稳定密切相关。我们评估了慢性和急性PAH暴露在两种人肺上皮细胞系A549和NC-H1975中诱导遗传毒性的机制。2015年8月（非雾霾期）和11月（雾霾期），我们在中国杭州浙江大学西溪校区采集了大气PAHs样本。在我们的研究中，我们确定车辆排放是主要的人为PAH来源。PAHs根据美国环境保护局方法TO-13A进行提取。我们发现慢性PAH暴露使肺细胞外源性代谢途径饱和，促进细胞间活性氧的产生和积累。细胞氧化还原状态的慢性改变导致DNA损伤和基因组不稳定。慢性PAH暴露还扰乱了细胞DNA损伤反应，诱导S期停滞并抑制细胞凋亡。PAH代谢和DNA损伤反应的失调改变了细胞内环境稳定，增加了细胞对后续PAH暴露的易感性，从而增加了基因组突变和不稳定的可能性。
