title: hOGG1(326), XRCC1(399) and XRCC3(241) polymorphisms influence micronucleus frequencies in human lymphocytes in vivo.
abstract: A pooled analysis of five biomonitoring studies was performed to assess the influence of hOGG1(326), XRCC1(399) and XRCC3(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(241) genotypes compared to their referent counterparts (P < 0.001) and (ii) carriers of the Met/Met XRCC3(241) genotype compared to Thr/Thr XRCC3(241) carriers, as far as they are non-exposed and bear the variant (Ser/Cys or Cys/Cys) hOGG1(326) genotype (P < 0.01). Significantly lower MN frequencies were observed in carriers of the variant hOGG1(326) genotype compared to Ser/Ser hOGG1(326) carriers in the subgroup of non-smokers with Thr/Thr XRCC3(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(399)genotype (P < 0.001). In contrast, a significant MN decrease with smoking was observed in referents carrying the Ser/Ser hOGG1(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.
authors.affiliation: Laboratorium voor Cellulaire Genetica, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussel, Belgium. rmateuca@vub.ac.be
authors.forename: Raluca A
authors.initials: RA
authors.lastname: Mateuca
authors.forename: Mathieu
authors.initials: M
authors.lastname: Roelants
authors.forename: Gwenaelle
authors.initials: G
authors.lastname: Iarmarcovai
authors.forename: Peter V
authors.initials: PV
authors.lastname: Aka
authors.forename: Lode
authors.initials: L
authors.lastname: Godderis
authors.forename: Annie
authors.initials: A
authors.lastname: Tremp
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonassi
authors.forename: Michael
authors.initials: M
authors.lastname: Fenech
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bergé-Lefranc
authors.forename: Micheline
authors.initials: M
authors.lastname: Kirsch-Volders
mesh_terms: D000328:Adult; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012907:Smoking; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human