Levels of PAH–DNA adducts in cord blood and cord tissue and the risk of fetal neural tube defects in a Chinese population

Abstract

Introduction Maternal exposure to polycyclic aromatic hydrocarbons (PAHs) has been shown to be associated with an elevated risk for neural tube defects (NTDs). In the human body, PAHs are bioactivated and the resultant reactive epoxides can covalently bind to DNA to form PAH-DNA adducts, which may, in turn, cause transcription errors, changes in gene expression or altered patterns of apoptosis. During critical developmental phases, these changes can result in abnormal morphogenesis. Objectives We aimed to examine the relationship between the levels of PAH-DNA adducts in cord blood and cord tissue and the risk of NTDs. Methods From 2010 to 2012, sixty NTD cases and 60 healthy controls were recruited from a population-based birth defects surveillance system in five counties of Shanxi Province in Northern China, where the emission of PAHs remains one of the highest in the country and PAHs exposure is highly prevalent. PAH-DNA adducts in cord blood of 15 NTD cases and 15 control infants, and in cord tissue of 60 NTD cases and 60 control infants were measured using the 32P-postlabeling method. Results PAH-DNA adduct levels in cord blood tend to be higher in the NTD group (28.5 per 108 nucleotides) compared with controls (19.7 per 108 nucleotides), although the difference was not statistically significant (P=0.377). PAH-DNA adducts in cord tissue were significantly higher in the NTD group (24.6 per 106 nucleotides) than in the control group (15.3 per 106 nucleotides), P=0.010. A positive dose-response relationship was found between levels of PAH-DNA adducts in cord tissue and the risk of NTDs (P=0.009). When the lowest tertile was used as the referent and potential confounding factors were adjusted for, a 1.03-fold (95% CI, 0.37–2.89) and 2.96-fold (95% CI, 1.16–7.58) increase in the risk of NTDs was observed for fetuses whose cord tissue PAH-DNA adduct levels were in the second and highest tertile, respectively. Conclusions High levels of PAH-DNA adducts in fetal tissues were associated with increased risks of NTDs.

Oxidative Stress and Apoptosis in Benzo[a]pyrene-Induced Neural Tube Defects

“…PAHs are ubiquitous environmental pollutants. Our [7] , [16] , [17] and other [14] epidemiological studies have suggested that maternal exposure to PAHs is associated with an elevated risk of NTDs in the offspring. However, evidence from animal experiments is limited.…”

“…Human epidemiological studies have found an association between higher concentrations of PAHs in the venous blood of pregnant women and placental tissue with an elevated risk for NTDs, with high molecular weight PAHs (h_PAHs) conferring a higher risk [7] , [16] . In addition, we found that higher levels of PAH-DNA adducts in foetal tissues were associated with increased risks of NTDs [17] . Thus, it was hypothesised that exposure to PAHs may be a causal event in the development of NTDs.…”

Air pollution, a rising environmental risk factor for cognition, neuroinflammation and neurodegeneration: The clinical impact on children and beyond

“…People's exposures to PAHs -complex mixtures containing over 100 compounds-are associated Prenatal PAHs exposures are harmful to the developing brain, high levels of PAH-DNA adducts in cord blood have been associated with neural tube defects, and occupational exposures during pregnancy increase the risk for small for gestational age babies [25][26][27]. In the U.S.…”

Neural Tube Defects and ZIC4 Hypomethylation in Relation to Polycyclic Aromatic Hydrocarbon Exposure

“…The developmental origins of health and disease hypothesis asserts that exposure to environmental pollutants during embryonic development, a critical period for epigenetic reprogramming, leads to epigenetic dysregulation, and results in increased disease risk (Heindel and Vandenberg, 2015). Several previous epidemiological studies support a positive association between maternal polycyclic aromatic hydrocarbon (PAHs) exposure and elevated risk for the development of NTDs in offspring, when PAHs or PAH-DNA adducts were used as exposure markers in maternal serum, placental tissue, cord blood, and cord tissue (Ren et al, 2011;Yuan et al, 2013;Wang et al, 2015;Yi et al, 2015). PAHs are common persistent organic pollutants in the environment formed during incomplete combustion of organic materials.…”