title: Characteristics of DNA methylation changes induced by traffic-related air pollution.
abstract: Traffic-related air pollution (TRAP) is a potential risk factor for numerous respiratory disorders, including lung cancer, while alteration of DNA methylation may be one of the underlying mechanisms. However, the effects of TRAP mixtures on DNA methylation have not been investigated. We have studied the effects of brief or prolonged TRAP exposures on DNA methylation in the rat. The exposures were performed in spring and autumn, with identical study procedures. In each season, healthy Wistar rats were exposed to TRAP at for 4 h, 7 d, 14 d, or 28 d. Global DNA methylation (LINE-1 and Alu) and specific gene methylation (p16(CDKN2A), APC, and iNOS) in the DNA from blood and lung tissues were quantified by pyrosequencing. Multiple linear regression was applied to assess the influence of air pollutants on DNA methylation levels. The levels of PM2.5, PM10, and NO2 in the high and moderate groups were significantly higher than in the control group. The DNA methylation levels were not significantly different between spring and autumn. When spring and autumn data were analyzed together, PM2.5, PM10, and NO2 exposures were associated with changes in%5mC (95% CI) in LINE-1, iNOS, p16(CDKN2A), and APC ranging from -0.088 (-0.150, -0.026) to 0.102 (0.049, 0.154) per 1 μg/m(3) increase in the pollutant concentration. Prolonged exposure to a high level of TRAP was negatively associated with LINE-1 and iNOS methylation, and positively associated with APC methylations in the DNA from lung tissues but not blood. These findings show that TRAP exposure is associated with decreased methylation of LINE-1 and iNOS, and increased methylation of p16(CDKN2A) and APC.
authors.affiliation: Environmental Epigenetics Laboratory, Department of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.affiliation: Environmental Epigenetics Laboratory, Department of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address: jinedu@zju.edu.cn.
authors.forename: Yongtang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Environmental Epigenetics Laboratory, Department of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Xinneng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiothoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Environmental Epigenetics Laboratory, Department of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Environmental Epigenetics Laboratory, Department of Environmental Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Institute of Pharmacology, Zhejiang University School of Pharmacology, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Yinchun
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000032:analysis; D000818:Animals; D019175:DNA Methylation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity; D011401:Promoter Regions, Genetic; D051381:Rats; D017208:Rats, Wistar; D012307:Risk Factors; D012621:Seasons
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: APC gene; Methylation; Particulate matter; Traffic-related air pollution