AbstractThe susceptibility of individuals to the genotoxic effect of pesticides can be modulated by genetic variations in the xenobiotic detoxification and DNA repair processes. This study evaluates if the two BER polymorphisms (XRCC1Arg194TrpandOGG1Ser326Cys) or the combined genotypes of these polymorphisms withPON1Gln192Argcould modify individual susceptibility to pesticide exposure in vineyard workers, as measured by micronucleus formation and DNA damage induction in peripheral leukocytes. The study population comprised 108 agricultural workers exposed to pesticides and 65 nonexposed. Our results demonstrate that individuals with the variant allele (OGG1Cys) showed higher DNA damage, detected by the comet assay, in relation to individuals carrying the wild‐typeOGG1Serallele. Considering the combined influence of metabolizingPON1and the DNA repairOGG1genes, we observed significantly higher DNA damage in the comet assay in the exposed group when a less efficientOGG1Cysallele was acting independently of thePON1genotype, reinforcing the importance of the OGG1 repair enzyme in the response to DNA damage by pesticide exposure. The association of thePONGln/Glngenotype with higher MN frequency suggests that thePON1genotype is a major determinant of genotoxic risk in individuals exposed to pesticides. Analysis of the compared effect ofXRCC1andPON1genotypes in the exposed group suggested that, among the poorly metabolizingPON1Gln/Glnindividuals, theXRCC1Arg/Trpgenotype has a protective effect with respect to MN formation. These results indicate that enhancedXRCC1function may provide some protection from the enhanced genotoxic risk associated with inefficient xenobiotic detoxification in the studied population. Environ. Mol. Mutagen. 52:20–27, 2011. © 2010 Wiley‐Liss, Inc.