Influence of hOGG1, XRCC1 and XRCC3 genotypes on biomarkers of genotoxicity in workers exposed to cobalt or hard metal dusts.
Identification of genetic polymorphisms responsible for reduced DNA repair capacity may allow better cancer prevention. We examined whether variations in genes involved in base-excision (hOGG1, XRCC1) and double strand break (XRCC3) DNA repair contribute to inter-individual differences in genotoxic effects induced in the lymphocytes of 21 cobalt (Co) exposed, 26 hard metal (WC-Co) exposed and 26 matched control male workers. Genotyping was performed by PCR-RFLP. DNA single strand breaks and alkali-labile sites were measured by the alkaline Comet assay. Chromosomal rearrangements resulting from chromosome loss or acentric fragments were assessed as micronucleated mononucleates (MNMC) and binucleates (MNCB) with the cytokinesis-block micronucleus test. Urinary 8-hydroxydeoxyguanosine (8-OHdG) levels were used as an indicator of systemic oxidative DNA damage. A significantly higher frequency of MNMC was observed in WC-Co exposed workers with variant hOGG1(326) genotype. Multivariate analysis performed with genotypes, age, exposure status, type of plant, smoking and their interaction terms as independent variables indicated that MNMC and Comet tail DNA (TD) were influenced by genetic polymorphisms. In the exposed and total populations, workers variant for both XRCC3 and hOGG1 had elevated MNMC frequencies. Further studies will demonstrate whether genotyping for hOGG1 and XRCC3 polymorphisms is useful for a better individual monitoring of workers.
Mateuca
R
R
Vrije Universiteit Brussel, Laboratorium voor Cellulaire Genetica, Pleinlaan 2, B-1050 Brussels, Belgium. rmateuca@vub.ac.be
Aka
P V
PV
De Boeck
M
M
Hauspie
R
R
Kirsch-Volders
M
M
Lison
D
D
D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers / Q000032:analysis; D003035:Cobalt / Q000633:toxicity*; D020552:Comet Assay; D004249:DNA Damage; D045647:DNA Glycosylases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D004391:Dust; D005838:Genotype; D006801:Humans; D008297:Male; D008670:Metals / Q000633:toxicity*; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D009152:Mutagenicity Tests; D016273:Occupational Exposure / Q000009:adverse effects*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D000076105:X-ray Repair Cross Complementing Protein 1
D015415:Biomarkers; D004268:DNA-Binding Proteins; D004391:Dust; D008670:Metals; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; D003035:Cobalt; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; D003849:Deoxyguanosine