title: Repair competence assay in studies of the influence of environmental exposure to c-PAHs on individual susceptibility to induction of DNA damage.
abstract: Previous results from studies performed in three European cities suggested a decrease in DNA repair efficiency observed in lymphocytes of subjects occupationally exposed to environmental carcinogenic polycyclic aromatic hydrocarbons (c-PAHs). The aim of this study was to investigate whether a relationship between exposure to environmental c-PAHs and cellular vulnerability to the induction of DNA damage and its repair is confirmed in a pooled group of subjects from Prague, Kosice and Sofia. The investigated pool consisted of 144 subjects occupationally exposed to environmental c-PAHs, who were municipal policemen or bus drivers. A control group of 115 matched individuals consisted of males unexposed at work to c-PAHs. The repair efficacy was evaluated by a comparison of the DNA damage detected by the single cell gel electrophoresis (SCGE) immediately after challenging the cells with X-ray irradiation, with residual damage (RD) being measured after an incubation period of 60min. A stochastic concept for a mechanism of the interaction between DNA and various genotoxic exposures, was applied to analyze a relationship between exposure and biological effect in the studied sample. The outcome of the study confirms that the exposure to environmental c-PAHs or smoking cigarettes, significantly decreases DNA repair efficiency (repair efficiency in the pooled group of exposed individuals was 61.8+/-11.8% versus 67.9+/-9.9 in control, p<0.001, and repair efficiency in group of smoking individuals was 63.0+/-11.5% versus 65.9+/-11.1 in nonsmokers, p<0.005). The repair efficiency can be affected by a genetic polymorphism, such as subjects with a homozygous mutation in polymorphic CYP1A1((Val/Val)) enzyme, or slow NAT2 acetylators, who showed a considerably lower DNA repair efficiency (i.e. average repair efficiency in subgroups of fast acetylators was for the control subgroup 68.1% versus 66.5% in exposed subjects, while in the case of subgroups of slow acetylators, for the control group was 68.0% versus significantly less in the exposed subjects, 60.6%, p<0.05). Smoking habits, or the diet's vitamin content, significantly affected the process. The results obtained confirm a potential value of the method as a biomarker of susceptibility in molecular epidemiology or preclinical studies, aimed at predicting susceptibility to various genotoxic exposures (environmental, occupational, therapeutic). To conclude, the research proved the influence of environmental c-PAHs, genotypes, and life styles on DNA damage and on its repair efficiency. Even low exposure to environmental c-PAHs altered DNA repair abilities of the subjects, which may result in an increased cancer risk. The findings confirm that c-PAHs should become pollutants that are subject to regulation.
authors.affiliation: Department of Radiation and Environmental Biology, The H. Niewodniczański Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Krakow, Poland. b7wasile@cyf-kr.edu.pl
authors.forename: Antonina
authors.initials: A
authors.lastname: Cebulska-Wasilewska
authors.forename: Blanka
authors.initials: B
authors.lastname: Binkova
authors.forename: Radim J
authors.initials: RJ
authors.lastname: Sram
authors.forename: Ivan
authors.initials: I
authors.lastname: Kalina
authors.forename: Teodor
authors.initials: T
authors.lastname: Popov
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics; D002274:Carcinogens, Environmental / Q000633:toxicity*; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D004249:DNA Damage; D004260:DNA Repair; D005838:Genotype; D006801:Humans; D008297:Male; D016273:Occupational Exposure; D016495:Police; D011084:Polycyclic Aromatic Hydrocarbons
chemical_list: D000393:Air Pollutants; D002274:Carcinogens, Environmental; D011084:Polycyclic Aromatic Hydrocarbons; D019363:Cytochrome P-450 CYP1A1; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human