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Part Fibre Toxicol. 2014 Dec 9;11:71. doi: 10.1186/s12989-014-0071-3.

Short-term diesel exhaust inhalation in a controlled human crossover study is associated with changes in DNA methylation of circulating mononuclear cells in asthmatics.

Author information

1
Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 west 28th Avenue, Vancouver, V5Z4H4, Canada. ruiwei06@gmail.com.
2
Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 west 28th Avenue, Vancouver, V5Z4H4, Canada. megjones@mail.ubc.ca.
3
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.
4
Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 west 28th Avenue, Vancouver, V5Z4H4, Canada. msk@cmmt.ubc.ca.
5
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.
6
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.

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.

CONCLUSION:

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.

PMID:
25487561
PMCID:
PMC4268899
DOI:
10.1186/s12989-014-0071-3
[Indexed for MEDLINE]
Free PMC Article

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