The role of XRCC1 polymorphisms in base excision repair of etheno-DNA adducts in French vinyl chloride workers

Details

• Personal Author:
  Brandt-Rauf P ; Freyer G ; Kanki C ; Li Y ; Marion M-J ; Santella R ; Zipprich J
• Description:
  OBJECTIVES: The purpose of this study was to examine whether polymorphisms in the XRCC1 DNA-repair protein can affect the base excision repair capacity to remove etheno-DNA adducts induced by vinyl chloride exposure that account for the occurrence of mutant biomarkers of effect seen in exposed workers. MATERIALS AND METHODS: Using polymerase chain reaction-restriction fragment length polymorphism and fluorescence polarization techniques, we examined the effect of three x-ray cross complementing-1 protein polymorphisms, at codons 194, 280 and 399, on the occurrence of mutant biomarkers in ras-p21 and p53 induced by vinyl chloride exposure in a cohort of 211 French vinyl chloride workers to correlate differences in genotype with differences in the presence of these biomarkers. Also, cell cultures of lymphoblast lines from a pair of individuals, one homozygous wild-type and one homozygous variant for the codon 399 polymorphism, were exposed to the reactive intermediate of vinyl chloride, and, using an enzyme-linked immunosorbent assay, levels of etheno-DNA adducts generated and repaired were measured and compared. RESULTS: After adjusting for age, smoking, alcohol drinking and cumulative vinyl chloride exposure, compared to workers who were homozygous wild-type for all alleles, the odds ratio for the presence of either biomarker increased to 2.0 (95% CI: 1.0-3.9) for workers with any one variant allele and to 2.4 (95% CI: 1.1-5.2) for workers with more than one variant allele. Data from the cell culture experiments indicating that repair of etheno-DNA adducts is considerably better in wild-type cells compared to polymorphic cells were supportive of the epidemiologic results. CONCLUSIONS: This study provides further evidence that polymorphisms in XRCC1 can be an important biomarker of susceptibility in populations exposed to agents that produce damage removed by base excision repair. Description provided by NIOSH
• Subjects:
  • Biomarkers
  • Enzymes
  • Epidemiology
  • Mutagens
  • Occupational Health
  • Safety
  • Workplace
• Keywords:
  • Proteins
  • Biomarkers
  • Mutation
  • Mutagens
  • Exposure-levels
  • Workers
  • Work-environment
  • Enzymatic-effects
  • Enzymes
  • Cellular-function
  More +
• ISSN:
  1232-1087
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  45-52
• Volume:
  19
• Issue:
  1
• NIOSHTIC Number:
  nn:20042197
• Citation:
  Int J Occup Med Environ Health 2006 Jan/Mar; 19(1):45-52
• Contact Point Address:
  Prof. P.W. Brandt-Rauf, Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, 60 Haven Avenue, New York, NY 10032
• Email:
  pwb1@columbia.edu
• CAS Registry Number:
  • Vinyl chloride (CAS RN 75-01-4)
• Federal Fiscal Year:
  2006
• Performing Organization:
  Department of Environmental Health Sciences, The Mailman School of Public Health, Columbia University, New York, New York
• Peer Reviewed:
  True
• Start Date:
  20010701
• Source Full Name:
  International Journal of Occupational Medicine and Environmental Health
• End Date:
  20150831
• Download URL:
  https://stacks.cdc.gov/view/cdc/194497/cdc_194497_DS1.pdf
• File Type:
  [PDF - 98.84 KB]
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8e9bfb10af2035e3368887b5deb79242b7e374b6624aa7b9a6f5a4606f6ea177643703b08af8e27b861776a79855c6d2710df4ddd53203e985ef9cc26d084dcf