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Background: Epidemiologic studies suggest that variability in DNA damage from vinyl chloride monomer (VCM) may be partially mediated by genetic polymorphisms in DNA repair. This study aimed to corroborate these observations with controlled experiments in vitro using cell lines from individuals with differing DNA repair genotypes to determine damage following VCM metabolite exposure. Methods: Matched pairs of lymphoblast cell lines (homozygous wild-type versus homozygous variant for either XRCC1 399 or XPD 751 polymorphism) were exposed to chloroacetaldehyde and analyzed by the cytokinesis-block micronucleus assay. Results: All cell lines demonstrated a dose-response of increasing micronuclei with increasing exposure, but for both XRCC1 and XPD, the polymorphic cells peaked at higher micronucleus frequencies and declined at a slower rate to baseline than the wild-type cells. Conclusion: This supports the findings that XRCC1 and XPD polymorphisms may result in deficient DNA repair of VCM-induced genetic damage. [ABSTRACT FROM AUTHOR]