title: Maternal exposure to polycyclic aromatic hydrocarbons and 5'-CpG methylation of interferon-γ in cord white blood cells.
abstract: BACKGROUND
  Maternal factors are implicated in the onset of childhood asthma. Differentiation of naïve CD4+ T lymphocytes into pro-allergic T-helper 2 cells induces interleukin (IL)4 expression and inhibits interferon (IFN)γ expression accompanied by concordant methylation changes in the promoters of these genes. However, it has yet to be established whether maternal exposure to polycyclic aromatic hydrocarbons (PAHs) can alter these gene promoters epigenetically during fetal development.
  
  
  OBJECTIVE
  In this study we sought to elucidate the relationship between maternal PAH exposure and promoter methylation status of IFNγ and IL4.
  
  
  METHODS
  We assessed the effects of benzo[a]pyrene (BaP), a representative airborne PAH, on the methylation status of the IFNγ and IL4 promoters in Jurkat cells and two lung adenocarcinoma cell lines, and on gene expression. In addition, we evaluated methylation status of the IFNγ promoter in cord white blood cells from 53 participants in the Columbia Center for Children's Environmental Health cohort. Maternal PAH exposure was estimated by personal air monitoring during pregnancy.
  
  
  RESULTS
  In vitro exposure of the cell models to low, noncytotoxic doses (0.1 and 1 nM) of BaP elicited increased promoter hypermethylation and reduced expression of IFNγ, but not IL4. IFNγ promoter methylation in cord white blood cells was associated with maternal PAH exposure in the cohort study subsample.
  
  
  CONCLUSIONS
  Consistent with the results for the cell lines, maternal exposure to PAHs was associated with hypermethylation of IFNγ in cord blood DNA from cohort children. These findings support a potential role of epigenetics in fetal reprogramming by PAH-induced environmental diseases.
authors.affiliation: Division of Environmental Genetics and Molecular Toxicology, College of Medicine, University of Cincinnati, Cincinnati, Ohio, USA.
authors.forename: Wan-yee
authors.initials: WY
authors.lastname: Tang
authors.forename: Linda
authors.initials: L
authors.lastname: Levin
authors.forename: Glenn
authors.initials: G
authors.lastname: Talaska
authors.forename: Yuk Yin
authors.initials: YY
authors.lastname: Cheung
authors.forename: Julie
authors.initials: J
authors.lastname: Herbstman
authors.forename: Deliang
authors.initials: D
authors.lastname: Tang
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Miller
authors.forename: Frederica
authors.initials: F
authors.lastname: Perera
authors.forename: Shuk-Mei
authors.initials: SM
authors.lastname: Ho
mesh_terms: D001483:Base Sequence; D018899:CpG Islands; D019175:DNA Methylation; D017931:DNA Primers; D005260:Female; D005312:Fetal Blood / Q000166:cytology*; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007958:Leukocyte Count; D018811:Maternal Exposure; D008969:Molecular Sequence Data; D011083:Polycyclic Compounds / Q000032:analysis / Q000633:toxicity*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D011083:Polycyclic Compounds; D007371:Interferon-gamma