Research Article Mitochondrial DNACopyNumber and Exposure to Polycyclic Aromatic Hydrocarbons

Background: Increased mitochondrial DNA copy number (mtDNAcn) is a biologic response to mtDNA damage and dysfunction, predictive of lung cancer risk. Polycyclic aromatic hydrocarbons (PAHs) are established lung carcinogens andmay causemitochondrial 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 noncurrent smoking coke-oven 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 alterationswere characterized throughmeasures of internal dose (urinary 1-pyrenol), target dose [anti-benzo[a]pyrene diolepoxide (anti-BPDE)–DNA adduct], genetic instability (micronuclei and telomere length), 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 mmol 1-pyrenol/mol creatinine) showed highermtDNAcn [geometricmeans (GM)of 1.06 (unadjusted) and1.07 (age-adjusted)] comparedwith 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), micronuclei (P < 0.001), and telomere length (P 0.053)] and epigenetic [i.e., p53 gene-specific promotermethylation (P < 0.001)] alterations in the nDNA. In thewhole study population, unadjusted and age-adjustedmtDNAcnwas positively correlatedwith 1-pyrenol (P 0.043 and 0.032) and anti-BPDE–DNA adducts (P 0.046 and 0.049). Conclusions:PAHexposure andPAH-related nDNAgenotoxicity are associatedwith increasedmtDNAcn. Impact: The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(10); 1722–9. 2013 AACR