title: Mitochondrial DNA copy number and exposure to polycyclic aromatic hydrocarbons.
abstract: 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 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 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 alterations were characterized through measures 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 μmol 1-pyrenol/mol creatinine) showed higher mtDNAcn [geometric means (GM) of 1.06 (unadjusted) and 1.07 (age-adjusted)] compared with 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 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.
  
  
  CONCLUSIONS
  The present study is suggestive of potential roles of mtDNAcn in PAH-induced carcinogenesis.
authors.affiliation: Authors' Affiliations: Occupational Health Section, Department of Cardiac, Thoracic, and Vascular Sciences, Università degli Studi di Padova; Sistema Epidemiologico Regione Veneto (SER), Padova; Department of Clinical Sciences and Community Health, University of Milan, Milano and Fondazione IRCSS Ca' Granda - Ospedale Maggiore Policlinico, Milan, Italy; Institute of Occupational Medicine and Environmental Health, Sosnowiec, Poland; and Department of Environmental Health and Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Sofia
authors.initials: S
authors.lastname: Pavanello
authors.forename: Laura
authors.initials: L
authors.lastname: Dioni
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hoxha
authors.forename: Ugo
authors.initials: U
authors.lastname: Fedeli
authors.forename: Danuta
authors.initials: D
authors.lastname: Mielzynska-Svach
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D003077:Coke / Q000506:poisoning; D004249:DNA Damage; D019175:DNA Methylation; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D019652:Extraction and Processing Industry; D018628:Gene Dosage; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000097:blood / Q000139:chemically induced / Q000235:genetics; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis*; D011084:Polycyclic Aromatic Hydrocarbons / Q000506:poisoning*; D055815:Young Adult
chemical_list: D003077:Coke; D004272:DNA, Mitochondrial; D011084:Polycyclic Aromatic Hydrocarbons