Interactions between exposure to environmental polycyclic aromatic hydrocarbons and DNA repair gene polymorphisms on bulky DNA adducts in human sperm.
BACKGROUND
Nucleotide 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.


RESULTS
Sperm 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
These 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.
Key Laboratory of Reproductive Medicine, School of Public Health, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Guixiang
G
Ji
Aihua
A
Gu
Yong
Y
Zhou
Xiangguo
X
Shi
Yankai
Y
Xia
Yan
Y
Long
Ling
L
Song
Shoulin
S
Wang
Xinru
X
Wang
D000328:Adult; D018736:DNA Adducts; D004260:DNA Repair / Q000235:genetics*; D004781:Environmental Exposure; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D011083:Polycyclic Compounds / Q000633:toxicity*; D011110:Polymorphism, Genetic; D013094:Spermatozoa / Q000187:drug effects* / Q000648:ultrastructure
D018736:DNA Adducts; D011083:Polycyclic Compounds