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

Authors
Wang-Q; Tan-H-S; Zhang-F; Sun-Y; Feng-N-N; Zhou-L-F; Ye-Y-J; Zhu-YL; Li-Y-L; Brandt-Rauf-PW; Shao-H; Xia-Z-L
Source
Mutat Res 2013 Jun; 754(1-2):7-14
NIOSHTIC No.
20042973
Abstract
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)o/oo showed higher micronucleus frequency than the unexposed workers (2.51+/-1.96)o/oo (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.
Keywords
Workers; Humans; Men; Women; Exposure-levels; Risk-factors; Chromosome-damage; Genes; Genetic-factors; Genetics; Toxicology; Toxic-effects; Monomers; Author Keywords: Vinyl chloride monomer; Chromosomal damage; Polymorphism; Base excision repair; Nucleotide excision repair
Contact
Zhao-lin Xia, Department of Occupational Health and Toxicology, Box 288, School of Public Health, Fudan University, Shanghai 200032, China
CODEN
MUREAV
CAS No.
75-01-4
Publication Date
20130614
Document Type
Journal Article
Email Address
zlxia@shmu.edu.cn
Funding Type
Grant
Fiscal Year
2013
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-004192; B20130805
Issue of Publication
1-2
ISSN
0027-5107
Source Name
Mutation Research
State
FL; IL
Performing Organization
University of Illinois
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