title: Increased urinary excretion of 8-oxo-2'-deoxyguanosine, a biomarker of oxidative DNA damage, in urban bus drivers.
abstract: Oxidative damage to DNA could be involved in the increased risk of cancer associated with exposure to polluted urban air, which contains a number of oxidants. CYP1A2 is induced by and metabolizes polyaromatic hydrocarbons (PAH) and aromatic amines and could modify effects of exposure to ambient air pollution. Similarly, DNA repair may be influenced by occupational and other exposures as well as modify the effect of DNA damaging agents. As part of a large investigation of the genotoxic burden to diesel exposed workers in transport sectors we studied oxidative DNA damage in 57 non-smoking bus drivers from the greater Copenhagen area. The drivers were studied on a workday and on a day off work. Comparisons were made between drivers from the central (n=30) and rural/suburban (n=27) areas of Copenhagen. The rate of oxidative DNA damage was estimated from 24 h urinary excretion of 8-oxo-2'-deoxyguanosine (8-oxodG), a repair product of the highly mutagenic oxidation of guanine in DNA or the cellular pool of GTP. CYP1A2 activity was estimated from the urinary excretion of metabolites of dietary caffeine. The DNA repair was estimated by unscheduled DNA synthesis (UDS) in mononuclear cells isolated on the workday. Repeated measures ANOVA and multifactorial ANCOVA with CYP1A2 activity, age and UDS as covariates were used for statistical evaluation. On the workday, the 8-oxodG excretion was 190+/-108 and 146+/-89 pmol/kg 24 h in the bus drivers from central and the suburban/rural areas Copenhagen, respectively (p<0.05). The 8-oxodG excretion was not significantly different between the workday and the day off. CYP1A2 activity was not affected by driving area but was correlated with the 8-oxodG excretion on the workday (r=0.53; p<0.05). UDS was not significantly affected by driving area or correlated with the 8-oxodG excretion. The increased excretion of 8-oxodG in bus drivers from central Copenhagen as compared with drivers from rural/suburban greater Copenhagen suggests that exposure to ambient air pollution causes oxidative damage to DNA. This effect may be modified by the activity of CYP1A2 or a coregulated enzyme.
authors.affiliation: Institute of Public Health and Department of Pharmacology, University of Copenhagen, Panum Institute 18-5, DK-2200, Copenhagen, Denmark. steffen.loft@farmakol.ku.dk
authors.forename: S
authors.initials: S
authors.lastname: Loft
authors.forename: H E
authors.initials: HE
authors.lastname: Poulsen
authors.forename: K
authors.initials: K
authors.lastname: Vistisen
authors.forename: L E
authors.initials: LE
authors.lastname: Knudsen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015415:Biomarkers / Q000652:urine*; D019388:Cytochrome P-450 CYP1A2 / Q000097:blood; D004247:DNA / Q000096:biosynthesis / Q000097:blood; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D003718:Denmark; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000502:physiology / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D016273:Occupational Exposure; D014186:Transportation; D014466:Ultraviolet Rays; D014504:Urban Health; D014505:Urban Population
chemical_list: D015415:Biomarkers; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D019388:Cytochrome P-450 CYP1A2; D003849:Deoxyguanosine