A combined analysis of XRCC1, XRCC3, GSTM1 and GSTT1 polymorphisms and centromere content of micronuclei in welders.
The aims of the present study were to assess clastogenic and aneugenic properties of welding fumes using fluorescent in situ hybridization (FISH) with a human pancentromeric DNA probe. The involvement of genetic polymorphisms in DNA repair genes (p.Arg399Gln of XRCC1 and p.Thr241Met of XRCC3) and in detoxification genes (GSTM1 and GSTT1) on the centromere content of micronuclei (MN) was also evaluated. This study included 27 male welders working without any collective protection device and a control group (n = 30). The welders showed significantly higher levels of chromosome/genome damage compared to the controls. The frequencies of MN and centromere-positive MN (C+MN) per 1,000 binucleated cells were significantly higher in the exposed group than in the control group (7.1 per thousand +/- 3.7 versus 4.9 per thousand +/- 1.8; P = 0.012 and 3.5 per thousand +/- 1.8 versus 2.4 per thousand +/- 1.2; P = 0.018, respectively, Mann-Whitney U-test). The centromere-negative MN (C-MN) frequency was higher in the exposed subjects than in the controls (3.6 per thousand +/- 3.4 versus 2.5 per thousand +/- 1.4), but the Mann-Whitney U-test did not yield a significant result. In the total population, the GSTM1 and GSTT1 polymorphisms significantly affected the frequencies of C-MN and C+MN defined by FISH. GSTM1 positive subjects showed an increased C-MN frequency and GSTT1 null subjects showed an elevated C+MN frequency. When GSTM1 and GSTT1 genotypes were included in multiple regression analysis, the effect of the occupational exposure could better be demonstrated; both C+MN and C-MN were significantly increased in the welders. Our results suggest that the combined analysis of genetic polymorphisms and centromeres in MN may improve the sensitivity of the micronucleus assay in detecting genotoxic effects.
Laboratoire de Biogénotoxicologie et Mutagenèse Environnementale, EA 1784; IFR PMSE 112, Facultés de Médecine et de Pharmacie, Université de la Méditerranée, Marseille, France. gwenaelle.iarmarcovai@medecine.univ-mrs.fr
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Iarmarcovai
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Sari-Minodier
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Orsière
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De Méo
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Gallice
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Bideau
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Iniesta
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Pompili
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Bergé-Lefranc
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Botta
D000328:Adult; D002503:Centromere / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D015162:Micronucleus Tests / Q000379:methods*; D009153:Mutagens; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012907:Smoking; D014896:Welding; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D009153:Mutagens; D000076105:X-ray Repair Cross Complementing Protein 1; C110901:X-ray repair cross complementing protein 3; C000619371:XRCC1 protein, human; C413545:glutathione S-transferase T1