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Neurotoxicology. 2015 Jan;46:73-8. doi: 10.1016/j.neuro.2014.12.003. Epub 2014 Dec 15.

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

Author information

  • 1Institute of Reproductive and Child Health and Ministry of Health Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China.
  • 2Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX 77030, USA.
  • 3Dell Pediatric Research Institute, Department of Nutritional Sciences, University of Texas at Austin, Austin, TX 78723, USA.
  • 4Institute of Reproductive and Child Health and Ministry of Health Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China; Dell Pediatric Research Institute, Department of Nutritional Sciences, University of Texas at Austin, Austin, TX 78723, USA.
  • 5Institute of Reproductive and Child Health and Ministry of Health Key Laboratory of Reproductive Health, Peking University, Beijing 100191, China; Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China. Electronic address: renag@pku.edu.cn.

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, 60 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 (32)P-postlabeling method.

RESULTS:

PAH-DNA adduct levels in cord blood tend to be higher in the NTD group (28.5 per 10(8) nucleotides) compared with controls (19.7 per 10(8) 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 10(6) nucleotides) than in the control group (15.3 per 10(6) 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.

KEYWORDS:

Cord blood; Cord tissue; DNA adducts; Neural tube defects (NTDs); Polycyclic aromatic hydrocarbons (PAHs)

PMID:
25522656
PMCID:
PMC4339482
DOI:
10.1016/j.neuro.2014.12.003
[PubMed - indexed for MEDLINE]
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