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The Role of XRCC1 Polymorphisms in Base Excision Repair of Etheno-Dna Adducts in French Vinyl Chloride Workers
Journal article   Peer reviewed

The Role of XRCC1 Polymorphisms in Base Excision Repair of Etheno-Dna Adducts in French Vinyl Chloride Workers

Yongliang Li, Marie-Jeanne Marion, Jennifer Zipprich, Greg Freyer, Regina Santella, Chisaka Kanki and Paul Brandt-Rauf
International journal of occupational medicine and environmental health, v 19(1), pp 45-52
01 Jun 2006
DOI: https://doi.org/10.2478/v10001-006-0006-9
PMID: 16881598

Abstract

Base excision repair DNA adducts Gene-environment interaction Mutations
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.

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