A pooled analysis of five biomonitoring studies was performed to assess the influence of hOGG1326, XRCC1399 and XRCC3241 gene polymorphisms on micronuclei (MN) frequency in human peripheral blood lymphocytes, as measured by the ex vivo/in vitro cytokinesis-block micronucleus (CBMN) assay. Each study addressed a type of occupational exposure potentially able to induce DNA strand breakage (styrene, ionising radiation, cobalt/hard metal, welding fumes and inorganic arsenite compounds), and therefore MN, as a result of base excision repair and double-strand break repair deficiencies. The effect of genotype, age, exposure to genotoxic agents and smoking habit on MN induction was determined using Poisson regression analysis in 171 occupationally exposed male workers and in 132 non-exposed male referents. The analysis of genotype-genotype, genotype-smoking and genotype-exposure interactions by linear combinations of parameters showed significantly higher MN frequencies in the following subsets: (i) occupationally exposed workers carrying either the Thr/Thr or the Thr/Met XRCC3241 genotypes compared to their referent counterparts (P <0.001) and (ii) carriers of the Met/Met XRCC3241 genotype compared to Thr/Thr XRCC3241 carriers, as far as they are non-exposed and bear the variant (Ser/Cys or Cys/Cys) hOGG1326 genotype (P <0.01). Significantly lower MN frequencies were observed in carriers of the variant hOGG1326 genotype compared to Ser/Ser hOGG1326 carriers in the subgroup of non-smokers with Thr/Thr XRCC3241 genotype (P <0.01). Stratified analysis by occupational exposure showed a significant MN increase with smoking in occupationally exposed carriers of the Arg/Gln XRCC1399genotype (P <0.001). In contrast, a significant MN decrease with smoking was observed in referents carrying the Ser/Ser hOGG1326 genotype (P <0.01). These findings provide evidence that the combination of different DNA repair genes and their interaction with environmental genotoxic agents may modulate MN induction. Understanding the complexity of the relationships between exposure, DNA repair and MN frequencies require larger scale studies and complementary biomarkers.
ASJC Scopus subject areas
- Health, Toxicology and Mutagenesis