title: Chromosomal aberrations in tire plant workers and interaction with polymorphisms of biotransformation and DNA repair genes.
abstract: We evaluated chromosomal aberrations in lymphocytes of 177 workers exposed to xenobiotics in a tire plant and in 172 controls, in relation to their genetic background. Nine polymorphisms in genes encoding biotransformation enzymes and nine polymorphisms in genes involved in main DNA repair pathways were investigated for possible modulation of chromosomal damage. Chromosomal aberration frequencies were the highest among exposed smokers and the lowest in non-smoking unexposed individuals (2.5+/-1.8% vs. 1.7+/-1.2%, respectively). The differences between groups (ANOVA) were borderline significant (F=2.6, P=0.055). Chromosomal aberrations were higher in subjects with GSTT1-null (2.4+/-1.7%) than in those with GSTT1-plus genotype (1.8+/-1.4%; F=7.2, P=0.008). Considering individual groups, this association was significant in smoking exposed workers (F=4.4, P=0.040). Individuals with low activity EPHX1 genotype exhibited significantly higher chromosomal aberrations (2.3+/-1.6%) in comparison with those bearing medium (1.7+/-1.2%) and high activity genotype (1.5+/-1.2%; F=4.7, P=0.010). Both chromatid- and chromosome-type aberration frequencies were mainly affected by exposure and smoking status. Binary logistic regression analysis revealed that frequencies of chromatid-type aberrations were modulated by NBS1 Glu185Gln (OR 4.26, 95%CI 1.38-13.14, P=0.012), and to a moderate extent, by XPD Lys751Gln (OR 0.16, 95%CI 0.02-1.25, P=0.081) polymorphisms. Chromosome-type aberrations were lowest in individuals bearing the EPHX1 genotype conferring the high activity (OR 0.38, 95%CI 0.15-0.98, P=0.045). Present results show that exposed individuals in the tire production, who smoke, exhibit higher chromosomal aberrations frequencies, and the extent of chromosomal damage may additionally be modified by relevant polymorphisms.
authors.affiliation: Department of Medical Biology, Comenius University Bratislava, Jessenius Faculty of Medicine, Malá hora 4, 03754 Martin, Slovak Republic.
authors.forename: Ludovit
authors.initials: L
authors.lastname: Musak
authors.forename: Pavel
authors.initials: P
authors.lastname: Soucek
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Erika
authors.initials: E
authors.lastname: Halasova
authors.forename: Veronika
authors.initials: V
authors.lastname: Polakova
authors.forename: Jana
authors.initials: J
authors.lastname: Slyskova
authors.forename: Simona
authors.initials: S
authors.lastname: Susova
authors.forename: Janka
authors.initials: J
authors.lastname: Buchancova
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Smerhovsky
authors.forename: Jana
authors.initials: J
authors.lastname: Sedikova
authors.forename: Gabriela
authors.initials: G
authors.lastname: Klimentova
authors.forename: Oto
authors.initials: O
authors.lastname: Osina
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
mesh_terms: D000328:Adult; D001336:Automobiles; D001711:Biotransformation; D016022:Case-Control Studies; D002617:Chemical Industry; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008214:Lymphocytes; D008297:Male; D016273:Occupational Exposure; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012408:Rubber; D015262:Xenobiotics; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics
chemical_list: D015262:Xenobiotics; D012408:Rubber; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D004851:Epoxide Hydrolases; C522330:EPHX1 protein, human; D051759:Xeroderma Pigmentosum Group D Protein; C497292:ERCC2 protein, human; D045643:DNA Repair Enzymes