PAH-DNA adducts in environmentally exposed population in relation to metabolic and DNA repair gene polymorphisms

• Published in: Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 2007-07, Vol.620 (1-2), p.49-61
• Main Authors: Binkova, B, Chvatalova, I, Lnenickova, Z, Milcova, A, Tulupova, E, Farmer, P B, Sram, R J
• Format: Article
• Language: English
• ISSN: 1386-1964; 0027-5107
• DOI: 10.1016/j.mrfmmm.2007.02.022

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 super(3) super(2)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 32-55 mu g /m super(3), PM2.5 27-38 mu g/m super(3), c-PAHs 18-22ng/m super(3); personal exposure to c-PAHs: 9.7ng/m super(3) versus 5.8ng/m super(3) (P