title: An acellular assay to assess the genotoxicity of complex mixtures of organic pollutants bound on size segregated aerosol. Part II: oxidative damage to DNA.
abstract: Ambient air particulate matter (atmospheric aerosol; PM) is an important factor in the development of various diseases. Oxidative stress is believed to be one of the mechanisms of action of PM on the human organism. The aim of our study was to investigate the ability of organic extracts of size segregated aerosol particles (EOM; three fractions of aerodynamic diameter 1-10μm, 0.5-1μm and 0.17-0.5μm) to induce oxidative damage to DNA in an in vitro acellular system of calf thymus (CT) DNA with and without S9 metabolic activation. PM was collected in the Czech Republic at four places with different levels of air pollution. Levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) tended to increase with decreasing sizes of PM. S9 metabolic activation increased the oxidative capacity of PM; mean levels of 8-oxodG/10(5) dG per 1000m(3) of air for samples with and without metabolic activation were 0.093 and 0.067, respectively (p<0.05). When results of oxidative damage to DNA were normalized per microgram of aerosol mass, mean levels of 8-oxodG/10(5) dG were 0.265 and 0.191, for incubation with and without S9 fraction, respectively (p<0.05). We observed a significant positive association between concentrations of polycyclic aromatic hydrocarbons (c-PAHs) bound to PM and levels of 8-oxodG/10(5) dG per 1000m(3) of air after metabolic activation of EOM samples (R=0.695, p<0.05). The correlation was weaker and non-significant for samples without metabolic activation (R=0.523, p=0.08). In conclusion, we showed that organic extracts of PM were able to induce oxidative damage to DNA in vitro; this ability was increased after S9 metabolic activation of EOM and with decreasing sizes of PM.
authors.affiliation: Laboratory of Genetic Ecotoxicology, Institute of Experimental Medicine AS CR, v.v.i., Videnska 1083, 142 20 Prague, Czech Republic. prossner@biomed.cas.cz
authors.forename: Pavel
authors.initials: P
authors.lastname: Rossner
authors.forename: Jan
authors.initials: J
authors.lastname: Topinka
authors.forename: Jan
authors.initials: J
authors.lastname: Hovorka
authors.forename: Alena
authors.initials: A
authors.lastname: Milcova
authors.forename: Jana
authors.initials: J
authors.lastname: Schmuczerova
authors.forename: Jiri
authors.initials: J
authors.lastname: Krouzek
authors.forename: Radim J
authors.initials: RJ
authors.lastname: Sram
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D002417:Cattle; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D009152:Mutagenicity Tests / Q000379:methods*; D010084:Oxidation-Reduction; D052638:Particulate Matter / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D051381:Rats; D018709:Statistics, Nonparametric
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; C427203:calf thymus DNA; D003849:Deoxyguanosine