Mitochondrial DNA Copy Number and Exposure to Polycyclic Aromatic Hydrocarbons
Menée en Pologne sur 46 travailleurs de l'industrie du charbon, non fumeurs réguliers, et sur 44 témoins, cette étude évalue l'association entre une exposition professionnelle à des hydrocarbures aromatiques polycycliques (impliqués dans la carcinogenèse du poumon), des altérations génétiques et le nombre de copies d'ADN mitochondrial dans les lymphocytes du sang périphérique
Background : Increased mitochondrial DNA copy numbe(mtDNAcn) is a biological response to mtDNA damage and dysfunction predictive of lung cancer risk. Polycyclic aromatic hydrocarbons(PAHs) are established lung carcinogens and may cause mitochondrial toxicity. Whether PAH exposure and PAH-related nuclear DNA(nDNA) genotoxic effects are linked with increased mtDNAcn has never been evaluated.
Methods : We investigated the effect of chronic exposure to PAHs on mtDNAcn in peripheral blood lymphocytes(PBLs) of 46 Polish male non-current smoking cokeoven workers and 44 matched controls, who were part of a group of 94 study individuals examined in our previous work. Subjects PAH exposure and genetic alterations were characterized through measures of internal dose (urinary 1-pyrenol), target dose [anti-benzo[a]pyrenediolepoxide (anti-BPDE)-DNA adduct], genetic instability (micronuclei, MN and telomere length [TL]) and DNA methylation [p53 promoter] in PBLs. mtDNAcn(MT/S) was measured using a validated real-time PCR method.
Results : Workers with PAH exposure above the median value (>3 μmol 1-pyrenol/mol creatinine) showed higher mtDNAcn [geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared to controls [GM 0.89 (unadjusted); 0.89 (age-adjusted)] (p=0.029 and 0.016), as well as higher levels of genetic and chromosomal [i.e. anti-BPDE-DNA adducts (p<0.001), MN (p<0.001) and TL (p=0.053)] and epigenetic [i.e., p53 gene-specific promoter methylation (p<0.001)] alterations in the nDNA. In the whole study population, unadjusted and age-adjusted mtDNAcn was positively correlated with 1-pyrenol (p=0.043 and 0.032) and anti-BPDE-DNA adducts (p=0.046 and 0.049).
Conclusions : PAH exposure and PAH-related nDNA genotoxicity are associated with increased mtDNAcn.
Impact:The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis.
http://cebp.aacrjournals.org/content/early/2013/07/24/1055-9965.EPI-13-0118.abstract 2013