title: PAH-DNA adducts in environmentally exposed population in relation to metabolic and DNA repair gene polymorphisms.
abstract: Epidemiologic studies indicate that prolonged exposure to particulate air pollution may be associated with increased risk of cardiovascular diseases and cancer in general population. These effects may be attributable to polycyclic aromatic hydrocarbons (PAHs) adsorbed to respirable air particles. It is expected that metabolic and DNA repair gene polymorphisms may modulate individual susceptibility to PAH exposure. This study investigates relationships between exposure to PAHs, polymorphisms of these genes and DNA adducts in group of occupationally exposed policemen (EXP, N=53, males, aged 22-50 years) working outdoors in the downtown area of Prague and in matched "unexposed" controls (CON, N=52). Personal exposure to eight carcinogenic PAHs (c-PAHs) was evaluated by personal samplers during working shift prior to collection of biological samples. Bulky-aromatic DNA adducts were analyzed in lymphocytes by (32)P-postlabeling assay. Polymorphisms of metabolizing (GSTM1, GSTP1, GSTT1, EPHX1, CYP1A1-MspI) and DNA repair (XRCC1, XPD) genes were determined by PCR-based RFLP assays. As potential modifiers and/or cofounders, urinary cotinine levels were analyzed by radioimmunoassay, plasma levels of vitamins A, C, E and folates by HPLC, cholesterol and triglycerides using commercial kits. During the sampling period ambient particulate air pollution was as follows: PM10 32-55microg/m(3), PM2.5 27-38microg/m(3), c-PAHs 18-22ng/m(3); personal exposure to c-PAHs: 9.7ng/m(3) versus 5.8ng/m(3) (P<0.01) for EXP and CON groups, respectively. The total DNA adduct levels did not significantly differ between EXP and CON groups (0.92+/-0.28adducts/10(8) nucleotides versus 0.82+/-0.23adducts/10(8) nucleotides, P=0.065), whereas the level of the B[a]P-"like" adduct was significantly higher in exposed group (0.122+/-0.036adducts/10(8) nucleotides versus 0.099+/-0.035adducts/10(8) nucleotides, P=0.003). A significant difference in both the total (P<0.05) and the B[a]P-"like" DNA adducts (P<0.01) between smokers and nonsmokers within both groups was observed. A significant positive association between DNA adduct and cotinine levels (r=0.368, P<0.001) and negative association between DNA adduct and vitamin C levels (r=-0.290, P=0.004) was found. The results of multivariate regression analysis showed smoking, vitamin C, polymorphisms of XPD repair gene in exon 23 and GSTM1 gene as significant predictors for total DNA adduct levels. Exposure to ambient air pollution, smoking, and polymorphisms of XPD repair gene in exon 6 were significant predictors for B[a]P-"like" DNA adduct. To sum up, this study suggests that polymorphisms of DNA repair genes involved in nucleotide excision repair may modify aromatic DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from c-PAHs exposure.
authors.affiliation: Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR and Health Institute of Central Bohemia, Vídenská 1083, 14220 Prague, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Binkova
authors.forename: Irena
authors.initials: I
authors.lastname: Chvatalova
authors.forename: Zdena
authors.initials: Z
authors.lastname: Lnenickova
authors.forename: Alena
authors.initials: A
authors.lastname: Milcova
authors.forename: Elena
authors.initials: E
authors.lastname: Tulupova
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
authors.forename: Radim J
authors.initials: RJ
authors.lastname: Sram
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D001205:Ascorbic Acid / Q000097:blood; D002274:Carcinogens, Environmental / Q000633:toxicity*; D018736:DNA Adducts / Q000032:analysis*; D004260:DNA Repair; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D016273:Occupational Exposure; D016495:Police; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism / Q000633:toxicity*; D011110:Polymorphism, Genetic
chemical_list: D000393:Air Pollutants; D001205:Ascorbic Acid; D002274:Carcinogens, Environmental; D018736:DNA Adducts; D005982:Glutathione Transferase; D008055:Lipids; D011084:Polycyclic Aromatic Hydrocarbons