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. Following 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. We explore 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 non-smoking 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 (B[a]P)-DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants.

Results and Conclusions: 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). 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.

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