title: Urban benzene exposure and oxidative DNA damage: influence of genetic polymorphisms in metabolism genes.
abstract: Benzene has been implicated as an environmental risk factor in leukaemia and other haematological diseases. Relationships between urban benzene exposure, oxidative DNA damage and polymorphisms in metabolism enzymes were examined in 40 volunteers living and working in Copenhagen. Personal exposures to benzene, toluene and methyl tert-butyl ether (MTBE) were monitored during a 5-day period. DNA damage was measured by 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in lymphocyte DNA and urine and by comet assay with use of fapyguanine glycosylase (FPG) and endonuclease III (ENDO). Excretion of the benzene metabolites trans,trans-muconic acid (ttMA) and S-phenylmercapturic acid (S-PMA) were measured in urine. Polymorphisms in glutathione-S-transferases T1 (GSTT1), M1 (GSTM1) and P1 (GSTP1) and NAD(P)H:quinone oxidoreductase (NQO) were determined. Median exposures to benzene, toluene and MTBE were 2.5, 18.7 and 0.86 microg/m(3). No significant correlations between external benzene exposure and any of the biomarkers were found. However, a significant correlation between S-PMA excretion and 8-oxodG in lymphocytes was found (R(s)=0.39). Men were found to excrete significantly more ttMA than the women did and ttMA excretion in men was found to be significantly associated with external benzene exposure (R=0.53, P=0.025). In addition, ttMA and S-PMA excretion was significantly higher in subjects with the NQO+/-genotype compared with subjects with the wild type (P=0.004 and P=0.011, respectively). Even though there are some limitations in this study due to the low range of benzene exposure and biomarker concentrations as well as a small number of subjects, these results could suggest that even at ambient concentrations exposure to benzene could have genotoxic effects in susceptible individuals.
authors.affiliation: Institute of Public Health, c/o Department of Pharmacology, The Panum Institute, room 18-5-32, Blegdamsvej 3, DK-2200 Copenhagen, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Sørensen
authors.forename: Henrik
authors.initials: H
authors.lastname: Skov
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
authors.forename: Ole
authors.initials: O
authors.lastname: Hertel
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
mesh_terms: D000328:Adult; D001554:Benzene / Q000009:adverse effects*; D015415:Biomarkers; D020552:Comet Assay; D004249:DNA Damage; D004785:Environmental Pollutants / Q000009:adverse effects*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D008214:Lymphocytes; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D011110:Polymorphism, Genetic; D016482:Urinalysis
chemical_list: D015415:Biomarkers; D004785:Environmental Pollutants; D005982:Glutathione Transferase; D001554:Benzene