title: Oxidatively damaged DNA and inflammation in the liver of dyslipidemic ApoE-/- mice exposed to diesel exhaust particles.
abstract: Epidemiological studies have shown that exposure to air pollution particles is associated with cardiovascular diseases, whereas the role in the initiation of atherosclerosis is unresolved. Atherosclerosis is considered to be an inflammatory disease that also involves oxidative stress. Here we investigated effects of oxidative stress elicited by diesel exhaust particles (DEP) in the aorta, liver, and lung of dyslipidemic ApoE(-/-) mice at the age when visual plaques appear in the aorta (11-13 weeks). DEP was administrated by intraperitoneal injection (0, 50, 500 and 5,000 microg DEP/kg bodyweight) in order to omit vascular effects secondary to pulmonary inflammation. The mice were killed either 6 or 24h after the administration. Inflammation was measured as the expression of inducible nitric oxide synthase (iNOS) and serum nitric oxide and DNA damage was measured by the comet assay. The expression of iNOS mRNA was increased in the liver 6h after the administration. The level of oxidized purine bases, determined as formamidopyrimidine DNA glycosylase sites was increased by 67% (95% CI: 11-124%) in the liver after 24h in the mice administrated with only 50 microg/kg bodyweight. However, there was no indication of systemic inflammation determined as the serum concentration of nitric oxide and iNOS expression, and DNA damage was not increased in the aorta. These observations indicate that intraperitoneal DEP injection does not induce inflammation or oxidatively damaged DNA in the lung and aorta, whereas a direct effect in terms of inflammation and oxidized DNA was observed in the liver of dyslipidemic ApoE(-/-) mice.
authors.affiliation: Institute of Public Health, Department of Occupational and Environmental Health, University of Copenhagen, Øster Farimagsgade 5, Building 5, 2nd Floor, 1014 Copenhagen K, Denmark.
authors.forename: Janne Kjærsgaard
authors.initials: JK
authors.lastname: Folkmann
authors.affiliation: Institute of Public Health, Department of Occupational and Environmental Health, University of Copenhagen, Øster Farimagsgade 5, Building 5, 2nd Floor, 1014 Copenhagen K, Denmark.
authors.forename: Lotte
authors.initials: L
authors.lastname: Risom
authors.affiliation: Institute of Public Health, Department of Occupational and Environmental Health, University of Copenhagen, Øster Farimagsgade 5, Building 5, 2nd Floor, 1014 Copenhagen K, Denmark.
authors.forename: Christian Stevns
authors.initials: CS
authors.lastname: Hansen
authors.affiliation: Institute of Public Health, Department of Occupational and Environmental Health, University of Copenhagen, Øster Farimagsgade 5, Building 5, 2nd Floor, 1014 Copenhagen K, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.affiliation: Institute of Public Health, Department of Occupational and Environmental Health, University of Copenhagen, Øster Farimagsgade 5, Building 5, 2nd Floor, 1014 Copenhagen K, Denmark. Electronic address: p.moller@pubhealth.ku.dk.
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics*; D050197:Atherosclerosis / Q000150:complications / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000235:genetics*; D020552:Comet Assay; D004249:DNA Damage; D050171:Dyslipidemias / Q000150:complications / Q000235:genetics*; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress / Q000235:genetics; D052638:Particulate Matter / Q000493:pharmacokinetics / Q000633:toxicity*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001057:Apolipoproteins E; D052638:Particulate Matter; D001335:Vehicle Emissions; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II