title: Prenatal exposure to polycyclic aromatic hydrocarbons, benzo[a]pyrene-DNA adducts, and genomic DNA methylation in cord blood.
abstract: BACKGROUND
  Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic environmental pollutants generated during incomplete combustion. After exposure and during metabolism, PAHs can form reactive epoxides that can covalently bind to DNA. These PAH-DNA adducts are established markers of cancer risk. PAH exposure has been associated with epigenetic alterations, including genomic cytosine methylation. Both global hypomethylation and hypermethylation of specific genes have been associated with cancer and other diseases in humans. Experimental evidence suggests that PAH-DNA adduct formation may preferentially target methylated genomic regions. Early embryonic development may be a particularly susceptible period for PAH exposure, resulting in both increased PAH-DNA adducts and altered DNA methylation.
  
  
  OBJECTIVE
  We explored whether prenatal exposure to PAHs is associated with genomic DNA methylation in cord blood and whether methylation levels are associated with the presence of detectable PAH-DNA adducts.
  
  
  METHODS
  In a longitudinal cohort study of nonsmoking women in New York City, we measured PAH exposure during pregnancy using personal air monitors, assessed PAH internal dose using prenatal urinary metabolites (in a subset), and quantified benzo[a]pyrene-DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants.
  
  
  RESULTS
  Prenatal PAH exposure was associated with lower global methylation in umbilical cord white blood cells (p = 0.05), but global methylation levels were positively associated with the presence of detectable adducts in cord blood (p = 0.01).
  
  
  CONCLUSIONS
  These observations suggest that PAH exposure was adequate to alter global methylation in our study population. Additional epidemiologic studies that can measure site-specific cytosine methylation and adduct formation will improve our ability to understand this complex molecular pathway in vivo.
authors.affiliation: Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, New York 10032, USA.
authors.forename: Julie B
authors.initials: JB
authors.lastname: Herbstman
authors.forename: Deliang
authors.initials: D
authors.lastname: Tang
authors.forename: Deguang
authors.initials: D
authors.lastname: Zhu
authors.forename: Lirong
authors.initials: L
authors.lastname: Qu
authors.forename: Andreas
authors.initials: A
authors.lastname: Sjödin
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Camann
authors.forename: Frederica P
authors.initials: FP
authors.lastname: Perera
mesh_terms: D000328:Adult; D001564:Benzo(a)pyrene; D018736:DNA Adducts / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D005312:Fetal Blood; D006801:Humans; D018811:Maternal Exposure; D009519:New York City; D011084:Polycyclic Aromatic Hydrocarbons / Q000097:blood*; D011247:Pregnancy
chemical_list: D018736:DNA Adducts; D011084:Polycyclic Aromatic Hydrocarbons; C056612:benzo(a)pyrene-DNA adduct; C095911:polycyclic aromatic hydrocarbons-DNA adduct; D001564:Benzo(a)pyrene