title: Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics.
abstract: BACKGROUND
  Changes in DNA methylation have been associated with traffic-related air pollution in observational studies, but the specific mechanisms and temporal dynamics therein have not been explored in a controlled study of asthmatics. In this study, we investigate short-term effects of diesel exhaust inhalation on DNA methylation levels at CpG sites across the genome in circulating blood in asthmatics.
  
  
  METHODS
  A double-blind crossover study of filtered air and diesel exhaust exposures was performed on sixteen non-smoking asthmatic subjects. Blood samples were collected pre-exposure, and then 6 and 30 hours post-exposure. Peripheral blood mononuclear cell DNA methylation was interrogated using the Illumina Infinium HumanMethylation450 Array. Exposure-related changes in DNA methylation were identified. In addition, CpG sites overlapping with Alu or LINE1 repetitive elements and candidate microRNA loci were also analyzed.
  
  
  RESULTS
  DNA methylation at 2827 CpG sites were affected by exposure to diesel exhaust but not filtered air; these sites enriched for genes involved in protein kinase and NFkB pathways. CpG sites with significant changes in response to diesel exhaust exposure primarily became less methylated, with a site residing within GSTP1 being among the significant hits. Diesel exhaust-associated change was also found for CpG sites overlapping with Alu and LINE1 elements as well as for a site within miR-21.
  
  
  CONCLUSIONS
  Short-term exposure to diesel exhaust resulted in DNA methylation changes at CpG sites residing in genes involved in inflammation and oxidative stress response, repetitive elements, and microRNA. This provides plausibility for the role of DNA methylation in pathways by which airborne particulate matter impacts gene expression and offers support for including DNA methylation analysis in future efforts to understand the interactions between environmental exposures and biological systems.
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 west 28th Avenue, Vancouver, V5Z4H4, Canada. ruiwei06@gmail.com.
authors.forename: Ruiwei
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 west 28th Avenue, Vancouver, V5Z4H4, Canada. megjones@mail.ubc.ca.
authors.forename: Meaghan J
authors.initials: MJ
authors.lastname: Jones
authors.affiliation: Air Pollution Exposure Laboratory, Chan-Yeung Centre for Occupational and Environmental Lung Disease, Department of Medicine, Division of Respiratory Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia, V5Z1L9, Canada. francesco.sava@hotmail.ca.
authors.forename: Francesco
authors.initials: F
authors.lastname: Sava
authors.affiliation: Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 west 28th Avenue, Vancouver, V5Z4H4, Canada. msk@cmmt.ubc.ca.|Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, 2206 East Mall, Vancouver, British Columbia, V6T1Z3, Canada. msk@cmmt.ubc.ca.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Kobor
authors.affiliation: Air Pollution Exposure Laboratory, Chan-Yeung Centre for Occupational and Environmental Lung Disease, Department of Medicine, Division of Respiratory Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia, V5Z1L9, Canada. carlsten@mail.ubc.ca.
authors.forename: Christopher
authors.initials: C
authors.lastname: Carlsten
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001249:Asthma / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D018899:CpG Islands / Q000187:drug effects*; D018592:Cross-Over Studies; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009043:Motor Activity; D018384:Oxidative Stress / Q000187:drug effects; D052638:Particulate Matter / Q000008:administration & dosage / Q000633:toxicity; D012091:Repetitive Sequences, Nucleic Acid / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*; D055815:Young Adult
chemical_list: D000393:Air Pollutants; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D052638:Particulate Matter; D001335:Vehicle Emissions