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

Details

• Personal Author:
  Brandt-Rauf PW ; Feng N-N ; Li Y-L ; Shao H ; Sun Y ; Tan H-S ; Wang Q ; Xia Z-L ; Ye Y-J ; Zhang F ; Zhou L-F ; Zhu YL
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Chromosomes Genetics Hazardous Substances Men Occupational Health Risk Assessment Risk Factors Safety Toxicology Women
• Keywords:
  Author Keywords: Vinyl Chloride Monomer Base Excision Repair Chromosomal Damage Chromosome-damage Exposure-levels Genes Genetic-factors Humans Monomers Nucleotide Excision Repair Polymorphism Risk-factors Toxic-effects Workers

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• ISSN:
  0027-5107
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Florida ; Illinois ; OSHA Region 4 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  7-14
• Volume:
  754
• Issue:
  1
• NIOSHTIC Number:
  nn:20042973
• Citation:
  Mutat Res 2013 Jun; 754(1-2):7-14
• Contact Point Address:
  Zhao-lin Xia, Department of Occupational Health and Toxicology, Box 288, School of Public Health, Fudan University, Shanghai 200032, China
• Email:
  zlxia@shmu.edu.cn
• CAS Registry Number:
  Vinyl chloride (CAS RN 75-01-4)
• Federal Fiscal Year:
  2013
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  True
• Start Date:
  20010701
• Source Full Name:
  Mutation Research
• End Date:
  20150831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:1b0f10848852e2de85d221852f5f0755255d5d0068e19d0ff8cf775f7d279c99c852c155a1a83e0529edd119eaac9e8ff34a8fdfd7eda68c01e1fc29c3bcc874
• Download URL:
  https://stacks.cdc.gov/view/cdc/195018/cdc_195018_DS1.pdf
• File Type:
  [PDF - 438.91 KB ]