Interactions between Exposure to Environmental Polycyclic Aromatic Hydrocarbons and DNA Repair Gene Polymorphisms on Bulky DNA Adducts in Human Sperm

Guixiang Ji,Yong Zhou,Aihua Gu,Yankai Xia,Xinru Wang,Yan Long,Shoulin Wang,Ling Song,Xiangguo Shi,Hongmei Wang

doi:10.1371/journal.pone.0013145

Abstract

BackgroundNucleotide excision repair (NER) and base excision repair (BER) are the primary mechanisms for repair of bulky adducts caused by chemical agents, such as PAHs. It is expected that polymorphisms in NER or BER genes may modulate individual susceptibility to PAHs exposure. Here, we evaluate the effects of PAHs exposure and polymorphisms in NER and BER pathway, alone or combined, on polycyclic aromatic hydrocarbon-DNA (PAH–DNA) adducts in human sperm.Methodology/Principal FindingsSperm PAH-DNA adducts were measured by immunofluorescent assay using flow cytometry in a sample of 465 infertile adults. Polymorphisms of XPA, XPD, ERCC1, XPF, and XRCC1 were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. The PAHs exposure was detected as urinary 1-hydroxypyrene (1-OHP) levels. In multivariate models adjusted for potential confounders, we observed that XRCC1 5′pUTR -T/C, Arg194Trp, Arg399Gln polymorphisms were associated with increased sperm adduct levels. Furthermore, the stratified analysis indicated that adverse effects of XRCC1 Arg194Trp, Arg399Gln polymorphisms on PAH-DNA adducts were detected only in the high PAHs exposure group.Conclusions/SignificanceThese findings provided the first evidence that polymorphisms of XRCC1 may modify sperm PAH-DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from PAHs exposure.

Highlights

Over the last two decades, there has been a growing concern regarding the progressive decline in male fertility [1,2]
Conclusions/Significance: These findings provided the first evidence that polymorphisms of XRCC1 may modify sperm PAHDNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from polycyclic aromatic hydrocarbons (PAHs) exposure
Whether genetic polymorphisms influence the susceptibility of human sperm DNA to toxicant-induced damage is largely unknown

Summary

Introduction

Over the last two decades, there has been a growing concern regarding the progressive decline in male fertility [1,2]. Our previous studies among Chinese men have assessed the non-occupational exposure to PAHs by measuring 1-OHP concentrations in urine. It is found that the median concentration of CR-adjusted 1-OHP in our study is almost 16-fold higher than those in U.S populations [6]. This result suggests that Chinese adult males are highly exposed to PAHs in the environment, and possess extremely high exposure levels, so the potential health hazard of PAHs deserves more attention in China. We evaluate the effects of PAHs exposure and polymorphisms in NER and BER pathway, alone or combined, on polycyclic aromatic hydrocarbon-DNA (PAH–DNA) adducts in human sperm

Methods

Results

Conclusion