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:
  Author Keywords: Base Excision Repair Cellular-function DNA Adducts Enzymatic-effects Exposure-levels Gene-environment Interaction Mutation Mutations Proteins Work-environment Workers

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• 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
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:8e9bfb10af2035e3368887b5deb79242b7e374b6624aa7b9a6f5a4606f6ea177643703b08af8e27b861776a79855c6d2710df4ddd53203e985ef9cc26d084dcf
• Download URL:
  https://stacks.cdc.gov/view/cdc/194497/cdc_194497_DS1.pdf
• File Type:
  [PDF - 98.84 KB ]