title: Linking exposure to environmental pollutants with biological effects.
abstract: Exposure to ambient air pollution has been associated with cancer. Ambient air contains a complex mixture of toxics, including particulate matter (PM) and benzene. Carcinogenic effects of PM may relate both to the content of PAH and to oxidative DNA damage generated by transition metals, benzene, metabolism and inflammation. By means of personal monitoring and biomarkers of internal dose, biologically effective dose and susceptibility, it should be possible to characterize individual exposure and identify air pollution sources with relevant biological effects. In a series of studies, individual exposure to PM(2.5), nitrogen dioxide (NO(2)) and benzene has been measured in groups of 40-50 subjects. Measured biomarkers included 1-hydroxypyrene, benzene metabolites (phenylmercapturic acid (PMA) and trans-trans-muconic acid (ttMA)), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) in urine, DNA strand breaks, base oxidation, 8-oxodG and PAH bulky adducts in lymphocytes, markers of oxidative stress in plasma and genotypes of glutathione transferases (GSTs) and NADPH:quinone reductase (NQO1). With respect to benzene, the main result indicates that DNA base oxidation is correlated with PMA excretion. With respect to exposure to PM, biomarkers of oxidative damage showed significant positive association with the individual exposure. Thus, 8-oxodG in lymphocyte DNA and markers of oxidative damage to lipids and protein in plasma associated with PM(2.5) exposure. Several types of DNA damage showed seasonal variation. PAH adduct levels, DNA strand breaks and 8-oxodG in lymphocytes increased significantly in the summer period, requiring control of confounders. Similar seasonal effects on strand breaks and expression of the relevant DNA repair genes ERCC1 and OGG1 have been reported. In the present setting, biological effects of air pollutants appear mainly related to oxidative stress via personal exposure and not to urban background levels. Future developments include personal time-resolved monitors for exposure to ultrafine PM and PM(2.5,) use of GPS, as well as genomics and proteomics based biomarkers.
authors.affiliation: Institute of Public Health, c/o Department of Pharmacology, The Panum Institute, room 18-5-32, University of Copenhagen, Blegdamsvej 3, DK-2200 Copenhagen, N, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Sørensen
authors.forename: Herman
authors.initials: H
authors.lastname: Autrup
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
authors.forename: Ole
authors.initials: O
authors.lastname: Hertel
authors.forename: Steen Solvang
authors.initials: SS
authors.lastname: Jensen
authors.forename: Peter
authors.initials: P
authors.lastname: Vinzents
authors.forename: Lisbeth E
authors.initials: LE
authors.lastname: Knudsen
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
mesh_terms: D000393:Air Pollutants / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage / Q000187:drug effects*; D004781:Environmental Exposure; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics
chemical_list: D000393:Air Pollutants; D002273:Carcinogens; D004785:Environmental Pollutants