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

2.50
Hdl Handle:
http://hdl.handle.net/10146/53733
Title:
The role of XRCC1 polymorphisms in base excision repair of etheno-DNA adducts in French vinyl chloride workers.
Authors:
Li, Yongliang; Marion, Marie-Jeanne; Zipprich, Jennifer; Freyer, Greg; Santella, Regina M.; Kanki, Chisaka; Brandt-Rauf, Paul W.
Abstract:
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.
Citation:
Int. J. Occup. Med. Environ. Health 2006, 19 (1):45-52
Journal:
International Journal of Occupational Medicine and Environmental Health
Issue Date:
2006
URI:
http://hdl.handle.net/10146/53733
PubMed ID:
16881598
Additional Links:
http://versita.metapress.com/content/h23077l416157148/?p=f7b8afc360144e8d9d81c58be85da6c9&pi=3; http://www.imp.lodz.pl/?p=/home_pl/oficyna/baza_czasopism/ijomeh/&articleId=18289&l=EN&lang=PL
Type:
Article
Language:
en
Description:
Biomarkers of individual susceptibility: field studies; Biomarkers of individual susceptibility: validation. Biomarker: polymorphisms in XRCC1 (codons 194, 280 and 399)Effect studied: DNA damageTissue/biological material/sample size: blood. Method of analysis: polymerase chain reaction-restriction fragment length polymorphism; fluorescence polarization techniques; enzyme-linked immunosorbent assay. Study design: cohort study. Study size: 211 vinyl chloride workers Impact on outcome (including dose-response): 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. KEYWORDS - CLASSIFICATION: Adult;Aged;Alleles;analysis;biomarkers of individual susceptibility: field studies;biomarkers of individual susceptibility: validation;blood;Codon;Cohort Studies;DNA Adducts;DNA Damage;DNA Repair;DNA-Binding Proteins;Environmental Health;field studies;France;genetic;genetics;Humans;Male;metabolism;Middle Aged;New York;Occupational Exposure;poisoning;Polymorphism,Genetic;Proteins;Public Health;Research;Vinyl Chloride;
ISSN:
1232-1087
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Yongliang-
dc.contributor.authorMarion, Marie-Jeanne-
dc.contributor.authorZipprich, Jennifer-
dc.contributor.authorFreyer, Greg-
dc.contributor.authorSantella, Regina M.-
dc.contributor.authorKanki, Chisaka-
dc.contributor.authorBrandt-Rauf, Paul W.-
dc.date.accessioned2009-03-10T11:45:33Z-
dc.date.available2009-03-10T11:45:33Z-
dc.date.issued2006-
dc.identifier.citationInt. J. Occup. Med. Environ. Health 2006, 19 (1):45-52en
dc.identifier.issn1232-1087-
dc.identifier.pmid16881598-
dc.identifier.urihttp://hdl.handle.net/10146/53733-
dc.descriptionBiomarkers of individual susceptibility: field studies; Biomarkers of individual susceptibility: validation. Biomarker: polymorphisms in XRCC1 (codons 194, 280 and 399)Effect studied: DNA damageTissue/biological material/sample size: blood. Method of analysis: polymerase chain reaction-restriction fragment length polymorphism; fluorescence polarization techniques; enzyme-linked immunosorbent assay. Study design: cohort study. Study size: 211 vinyl chloride workers Impact on outcome (including dose-response): 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. KEYWORDS - CLASSIFICATION: Adult;Aged;Alleles;analysis;biomarkers of individual susceptibility: field studies;biomarkers of individual susceptibility: validation;blood;Codon;Cohort Studies;DNA Adducts;DNA Damage;DNA Repair;DNA-Binding Proteins;Environmental Health;field studies;France;genetic;genetics;Humans;Male;metabolism;Middle Aged;New York;Occupational Exposure;poisoning;Polymorphism,Genetic;Proteins;Public Health;Research;Vinyl Chloride;en
dc.description.abstractOBJECTIVES: 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.en
dc.language.isoenen
dc.relation.urlhttp://versita.metapress.com/content/h23077l416157148/?p=f7b8afc360144e8d9d81c58be85da6c9&pi=3en
dc.relation.urlhttp://www.imp.lodz.pl/?p=/home_pl/oficyna/baza_czasopism/ijomeh/&articleId=18289&l=EN&lang=PLen
dc.subjectBase excision repairen
dc.subjectMutationsen
dc.subjectDNA adductsen
dc.subjectGene-environment interactionen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshCodon-
dc.subject.meshCohort Studies-
dc.subject.meshDNA Adducts-
dc.subject.meshDNA Damage-
dc.subject.meshDNA Repair-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshFrance-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshOccupational Exposure-
dc.subject.meshPolymorphism, Genetic-
dc.subject.meshVinyl Chloride-
dc.titleThe role of XRCC1 polymorphisms in base excision repair of etheno-DNA adducts in French vinyl chloride workers.en
dc.typeArticleen
dc.identifier.journalInternational Journal of Occupational Medicine and Environmental Healthen

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