hOGG1 super(326), XRCC1 super(399) and XRCC3 super(241) polymorphisms influence micronucleus frequencies in human lymphocytes in vivo

• Published in: Mutagenesis 2008-01, Vol.23 (1), p.35-41
• Main Authors: Mateuca, Raluca A, Roelants, Mathieu, Iarmarcovai, Gwenaelle, Aka, Peter V, Godderis, Lode, Tremp, Annie, Bonassi, Stefano, Fenech, Michael, Berge-Lefranc, Jean-Louis, Kirsch-Volders, Micheline
• Format: Article
• Language: English
• ISSN: 0267-8357; 1464-3804

A pooled analysis of five biomonitoring studies was performed to assess the influence of hOGG1 super(326), XRCC1 super(399) and XRCC3 super(241) 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 XRCC3 super(241) genotypes compared to their referent counterparts (P < 0.001) and (ii) carriers of the Met/Met XRCC3 super(241) genotype compared to Thr/Thr XRCC3 super(241) carriers, as far as they are non-exposed and bear the variant (Ser/Cys or Cys/Cys) hOGG1 super(326) genotype (P < 0.01). Significantly lower MN frequencies were observed in carriers of the variant hOGG1 super(326) genotype compared to Ser/Ser hOGG1 super(326) carriers in the subgroup of non-smokers with Thr/Thr XRCC3 super(241) genotype (P < 0.01). Stratified analysis by occupational exposure showed a significant MN increase with smoking in occupationally exposed carriers of the Arg/Gln XRCC1 super(399)genotype (P < 0.001). In contrast, a significant MN decrease with smoking was observed in referents carrying the Ser/Ser hOGG1 super(326) 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.