Effects of airborne pollutants on mitochondrial DNA Methylation

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. © 2013 byun et al.; licensee biomed central ltd.