Title | DNA damage, serum metabolomic alteration and carcinogenic risk associated with low-level air pollution* |
Authors | Xu, Jiayu Liu, Yu Zhang, Qiaojian Su, Zekang Yan, Tenglong Zhou, Shupei Wang, Tiancheng Wei, Xuetao Chen, Zhangjian Hue, Guiping Chen, Tian Jia, Guang |
Affiliation | Peking Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth Sci, Beijing 100083, Peoples R China Peking Univ, Dept Lab Anim Sci, Hlth Sci Ctr, Beijing 100083, Peoples R China Third Hosp Peking Univ, Dept Clin Lab, Beijing 100083, Peoples R China Peking Univ, Sch Publ Hlth, Dept Toxicol, Beijing 100083, Peoples R China Beihang Univ, Sch Med Sci & Engn, Beijing 100191, Peoples R China Capital Med Univ, Sch Publ Hlth, Beijing 100069, Peoples R China Capital Med Univ, Beijing Key Lab Environm Toxicol, Beijing 100069, Peoples R China |
Keywords | POLYCYCLIC AROMATIC-HYDROCARBONS OXIDATIVE STRESS MITOCHONDRIAL DYSFUNCTION SPHINGOLIPID METABOLISM RESIDENTIAL AREA CANCER-RISK AMBIENT AIR BIOMARKER DISEASE PM2.5 |
Issue Date | 15-Mar-2022 |
Publisher | ENVIRONMENTAL POLLUTION |
Abstract | Outdoor air pollution has been classified as carcinogenic to humans (Group 1) for lung cancer, but the underlying mechanism and key toxic components remain incompletely understood. Since DNA damage and metabolite alterations are associated with cancer progression, exploring potential mechanisms linking air pollution and cancer might be meaningful. In this study, a real-time ambient air exposure system was established to simulate the realworld environment of adult male SD rats in Beijing from June 13th, 2018, to October 8th, 2018. 8-OHdG in the urine, gamma-H2AX in the lungs and mtDNA copy number in the peripheral blood were analyzed to explore DNA damage at different levels. Serum non-targeted metabolomics analysis was performed. Pair-wise spearman was used to explore the correlation between DNA damage biomarkers and serum differential metabolites. Carcinogenic risks of heavy metals and PAHs via inhalation were assessed according to US EPA guidelines. Results showed that PM2.5 and O3 were the major air pollutants in the exposure group and not detected in the control group. Compared with control group, higher levels of 8-OHdG, mtDNA copy number, gamma-H2AX and PCNA-positive nuclei cells were observed in the exposure group. Histopathological evaluation suggested ambient air induced alveolar wall thickening and inflammatory cell infiltration in lungs. Perturbed metabolic pathways identified included glycolysis/gluconeogenesis metabolism, purine and pyrimidine metabolism, etc. gamma-H2AX was positively correlated with serum ADP, 3-phospho-D-glyceroyl phosphate and N-acetyl-D-glucosamine. The BaPeq was 0.120 ng/m3. Risks of Cr(VI), As, V, BaP, BaA and BbF were above 1 x 10-6. We concluded that low-level air pollution was associated with DNA damage and serum metabolomic alterations in rats. Cr(VI) and BaP were identified as key carcinogenic components in PM2.5. Our results provided experimental evidence for hazard identification and risk assessment of low-level air pollution. |
URI | http://hdl.handle.net/20.500.11897/638455 |
ISSN | 0269-7491 |
DOI | 10.1016/j.envpol.2021.118763 |
Indexed | EI SCI(E) |
Appears in Collections: | 公共卫生学院 第三医院 |