Abstract:
Objective To explore the association between polymorphisms in nucleotide excision repair (NER) pathway genes and vinyl chloride (VC)-induced chromosomal damage in peripheral blood lymphocytes.
Methods Cytokinesis-block micronucleus (CBMN) assay was used to detect chromosomal damage in peripheral lymphocytes of 317 VC-exposed workers and 166 controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect 7 single nucleotide polymorphisms (SNPs) of 5 critical genes in NER pathways. The associations of these polymorphisms with chromosomal damage as well as the gene-exposure interaction were then analyzed.
Results The mean micronucleus frequency in the exposure group was (3.47& #177;2.65)‰, which was higher than that of the control workers(2.51& #177;1.96)‰ (P<0.01). The SNPs of XPA Ala23Gly, XPC Ala499Val, XPC Lys939Gln, and XPF 5'-UTR T2063A were associated with the micronucleus (MN) frequency as an indicator of susceptibility (FR and 95%CI:1.20, 1.05-1.39; 1.17, 1.04-1.32; 1.23, 1.09-1.38; 0.75, 0.64-0.91, all P<0.01, respectively), and interacted with VC cumulated exposure doses. Moreover, the results of haplotype analysis showed higher MN frequencies in the workers carrying the PAT-CG/PAT-TG, PAT+TG/PAT+TG, PAT+CA/PAT+CA or PAT+TG/PAT+TA diplotype than the workers carrying the wild-type PAT-CA/PAT-CA (FR and 95%CI:2.45, 2.01-3.75; 1.08, 1.02-1.32; 1.35, 1.13-1.57; 1.57, 1.02-1.96, P<0.01 or P<0.05, respectively); while the workers with PAT-CA/PAT+CA had lowered risks of the studied damage (FR=0.25, 95%CI:0.12-0.57, P<0.01).
Conclusion VC can induce chromosomal damage even when the exposure level is lower than the national occupational health standard of China. The polymorphism of DNA repair genes in NER pathway may be associated with chromosomal damage induced by VC.
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