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, 120 (5), 733-8

Prenatal Exposure to Polycyclic Aromatic Hydrocarbons, benzo[a]pyrene-DNA Adducts, and Genomic DNA Methylation in Cord Blood

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Prenatal Exposure to Polycyclic Aromatic Hydrocarbons, benzo[a]pyrene-DNA Adducts, and Genomic DNA Methylation in Cord Blood

Julie B Herbstman et al. Environ Health Perspect.

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.

Conflict of interest statement

The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention.

The authors declare they have no actual or potential competing financial interests.

Figures

Figure 1
Figure 1
Conceptual association between exposure measures and biomarkers along the toxicologic paradigm. Indicators of exposure include airborne BaP and other PAHs and dietary sources of PAHs. Biomarkers of internal dose include 1-OH-pyrene metabolites. Biomarkers of biologically effective dose include global DNA methylation and PAH–DNA adducts.
Figure 2
Figure 2
Global DNA methylation in cord blood according to prenatal air PAH exposure (based on univariate analyses). “High” and “Low” represent the geometric mean methylation (and 95% CIs) for those with prenatal concentrations above and below the median, respectively.
Figure 3
Figure 3
Probability of detectable BaP–DNA adducts as a function of global methylation in cord blood (based on univariate association). Circles represent the predicted probability of adduct detection based on logistic regression analyses where global methylation is an independent predictor; + indicates observed methylation at y = 0 for those without detectable adducts and at y = 1 for those with detectable adducts.

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