title: Effects of airborne pollutants on mitochondrial DNA methylation.
abstract: BACKGROUND
  Mitochondria have small mitochondrial DNA (mtDNA) molecules independent from the nuclear DNA, a separate epigenetic machinery that generates mtDNA methylation, and are primary sources of oxidative-stress generation in response to exogenous environments. However, no study has yet investigated whether mitochondrial DNA methylation is sensitive to pro-oxidant environmental exposures.
  
  
  METHODS
  We sampled 40 male participants (20 high-, 20 low-exposure) from each of three studies on airborne pollutants, including investigations of steel workers exposed to metal-rich particulate matter (measured as PM1) in Brescia, Italy (Study 1); gas-station attendants exposed to air benzene in Milan, Italy (Study 2); and truck drivers exposed to traffic-derived Elemental Carbon (EC) in Beijing, China (Study 3). We have measured DNA methylation from buffy coats of the participants. We measured methylation by bisulfite-Pyrosequencing in three mtDNA regions, i.e., the transfer RNA phenylalanine (MT-TF), 12S ribosomal RNA (MT-RNR1) gene and "D-loop" control region. All analyses were adjusted for age and smoking.
  
  
  RESULTS
  In Study 1, participants with high metal-rich PM1 exposure showed higher MT-TF and MT-RNR1 methylation than low-exposed controls (difference = 1.41, P = 0.002); MT-TF and MT-RNR1 methylation was significantly associated with PM1 exposure (beta = 1.35, P = 0.025); and MT-RNR1 methylation was positively correlated with mtDNA copy number (r = 0.36; P = 0.02). D-loop methylation was not associated with PM1 exposure. We found no effects on mtDNA methylation from air benzene (Study 2) and traffic-derived EC exposure (Study 3).
  
  
  CONCLUSIONS
  Mitochondrial MT-TF and MT-RNR1 DNA methylation was associated with metal-rich PM1 exposure and mtDNA copy number. Our results suggest that locus-specific mtDNA methylation is correlated to selected exposures and mtDNA damage. Larger studies are needed to validate our observations.
authors: Laboratory of Environmental Epigenetics, Exposure Epidemiology and Risk Program, Harvard School of Public Health, Boston, MA 02115, USA. hmbyun@hsph.harvard.edu
authors: Hyang-Min
authors: HM
authors: Byun
authors: Tommaso
authors: T
authors: Panni
authors: Valeria
authors: V
authors: Motta
authors: Lifang
authors: L
authors: Hou
authors: Francesco
authors: F
authors: Nordio
authors: Pietro
authors: P
authors: Apostoli
authors: Pier Alberto
authors: PA
authors: Bertazzi
authors: Andrea A
authors: AA
authors: Baccarelli
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000397:Air Pollution; D001483:Base Sequence; D001554:Benzene / Q000009:adverse effects; D002681:China; D019175:DNA Methylation / Q000187:drug effects*; D004272:DNA, Mitochondrial / Q000187:drug effects* / Q000378:metabolism; D018628:Gene Dosage; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D007558:Italy; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016273:Occupational Exposure / Q000009:adverse effects; D052638:Particulate Matter / Q000009:adverse effects; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013232:Steel / Q000009:adverse effects; D001335:Vehicle Emissions / Q000633:toxicity
chemical_list: D000395:Air Pollutants, Occupational; D004272:DNA, Mitochondrial; D052638:Particulate Matter; D001335:Vehicle Emissions; D013232:Steel; D001554:Benzene
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