Global and gene-specific promoter methylation changes are related to anti-B[a]PDE-DNA adduct levels and influence micronuclei levels in polycyclic aromatic hydrocarbon-exposed individuals

Int J Cancer. 2009 Oct 1;125(7):1692-7. doi: 10.1002/ijc.24492.

Abstract

We investigated the effect of chronic exposure to polycyclic aromatic hydrocarbons (PAHs) on DNA methylation states (percentage of methylated cytosines (%mC)) in Polish male nonsmoking coke-oven workers and matched controls. Methylation states of gene-specific promoters (p53, p16, HIC1 and IL-6) and of Alu and LINE-1 repetitive elements, as surrogate measures of global methylation, were quantified by pyrosequencing in peripheral blood lymphocytes (PBLs). DNA methylation was evaluated in relation to PAH exposure, assessed by urinary 1-pyrenol and anti-benzo[a]pyrene diolepoxide (anti-B[a]PDE)-DNA adduct levels, a critical genetic damage from B[a]P. We also evaluated whether PAH-induced DNA methylation states were in turn associated with micronuclei in PBLs, an indicator of chromosomal instability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Biomarkers / blood
  • Biomarkers / urine
  • Case-Control Studies
  • Coke*
  • DNA Adducts / blood*
  • DNA Methylation*
  • Genes, p53
  • Humans
  • Inhalation Exposure
  • Kruppel-Like Transcription Factors
  • Linear Models
  • Male
  • Micronuclei, Chromosome-Defective*
  • Middle Aged
  • Molecular Sequence Data
  • Occupational Exposure / adverse effects*
  • Poland
  • Polycyclic Aromatic Hydrocarbons / toxicity*
  • Polymerase Chain Reaction
  • Promoter Regions, Genetic*
  • Sequence Analysis, DNA

Substances

  • Biomarkers
  • Coke
  • DNA Adducts
  • HIC1 protein, human
  • Kruppel-Like Transcription Factors
  • Polycyclic Aromatic Hydrocarbons