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Polymorphisms in BER and NER pathway genes: Effects on micronucleus frequencies among vinyl chloride-exposed workers in northern China
Journal article   Peer reviewed

Polymorphisms in BER and NER pathway genes: Effects on micronucleus frequencies among vinyl chloride-exposed workers in northern China

Qi Wang, Hong-shan Tan, Fang Zhang, Yuan Sun, Nan-nan Feng, Li-fang Zhou, Yun-jie Ye, Yi-liang Zhu, Yong-liang Li, Paul W. Brandt-Rauf, …
Mutation research. Genetic toxicology and environmental mutagenesis, v 754(01-02), pp 7-14
14 Jun 2013
PMID: 23562908

Abstract

Base excision repair Chromosomal damage Nucleotide excision repair Polymorphism Vinyl chloride monomer
•Results showed higher micronucleus frequencies in exposed workers than control.•Gene polymorphism was associated with higher level of induced chromosome damage.•Results exhibited combined effect of repair gene polymorphism and exposure dose. In this study, a group of 317 workers occupationally exposed to vinyl chloride monomer and 166 normal, unexposed referents in Shandong province (Northern China) were examined for chromosomal damage in peripheral lymphocytes using the cytokinesis-blocked micronucleus (CB-MN) assay. The exposure group (3.47±2.65)‰ showed higher micronucleus frequency than the unexposed workers (2.51±1.96)‰ (P<0.01). We explored the relationship between genetic polymorphisms of XRCC1 (−77C/T, Arg194Trp, Arg280His, Arg399Gln), APE1 Asp148Glu, XPA Ala23Gly, XPC.PAT, XPC Ala499Val, XPC Lys939Gln, XPF 5′-UTR T2063A, XPG Exon15 G-C, ERCC13′-UTR C8092A and susceptibility of chromosomal damage in all the subjects. It was found that XRCC1 −77, XRCC1 280, APE1148, XPC.PAT, XPG Exon15 G-C, and ERCC13′-UTR C8092A polymorphisms showed no significant associations with micronucleus frequency in unexposed workers. However, among the exposed workers individuals with XRCC1 (−77C/T, Arg194Trp, Arg280His, Arg399Gln) polymorphisms had a significantly higher micronucleus frequency as seen in mean frequency ratios (FR) compared with their homozygous wild-type genotypes (FR=1.21, 95% CI: 1.05–1.39; P<0.01); (FR=1.14, 95% CI: 1.00–1.38; P<0.05) and (FR=1.26, 95% CI: 1.11–1.44; P<0.01); (FR=1.23, 95% CI: 1.08–1.46; P<0.01). Four SNP sites in the nucleotide excision repair (NER) pathway were associated with susceptibility for MN frequency in either unexposed or exposed workers. Further, we observed the gene–MN association changed with exposure for XRCC1 (−77C/T, Arg194Trp, Arg280His, Arg399Gln), XPA Ala23Gly, XPC Ala499Val, XPC Lys939Gln, XPF 5′-UTR T2063A. Moreover, Individuals carrying the XPC (PAT)-(499)-(939) diplotype, PAT-CG/PAT-TG, had a higher MN frequency, compared with individuals carrying the wild-type PAT-CA/PAT-CA.

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Collaboration types
Domestic collaboration
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Web of Science research areas
Biotechnology & Applied Microbiology
Genetics & Heredity
Toxicology
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