title: Oxidatively damaged DNA in aging dyslipidemic ApoE-/- and wild-type mice.
abstract: The free radical theory of aging depicts an accumulation of cellular oxidatively damaged DNA. In this study, we investigated this theory in mice with knocked-out apolipoprotein E gene (ApoE(-/-)), which develops atherosclerosis and wild-type counterparts. The level of oxidatively damaged DNA was investigated as strand breaks, endonuclease III- and formamidopyrimidine DNA glycosylase-sensitive sites by the comet assay. The level of DNA damage was mainly increased with age in the liver of ApoE(-/-) mice, whereas no increase was observed in the aorta or lung of the mice. This suggests that the accumulation of oxidized DNA in the liver of dyslipidemic ApoE(-/-) mice could be secondary to dysfunction of the lipid metabolism. Visually, the aortas of the ApoE(-/-) mice were clearly atherosclerotic as indicated by rigid texture and yellowish in color. However, the unaltered levels of oxidized DNA in severely atherosclerotic aortas of old ( approximately 70 weeks) ApoE(-/-) mice indicate that oxidative stress may not be a generalized phenomenon, but rather related locally to the individual plaques. In conclusion, the results of this study suggest that dyslipidemic ApoE(-/-) mice suffer from hepatic oxidative stress in terms of oxidized DNA, and this effect could be due to the dysfunction of lipid metabolism.
authors.affiliation: Department of Occupational and Environmental Health, Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5, building 5, 2nd floor, 1014 Copenhagen K, Denmark.
authors.forename: Janne Kjaersgaard
authors.initials: JK
authors.lastname: Folkmann
authors.forename: Steffen
authors.initials: S
authors.lastname: Loft
authors.forename: Peter
authors.initials: P
authors.lastname: Møller
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics*; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D050171:Dyslipidemias / Q000235:genetics*; D004720:Endonucleases / Q000378:metabolism; D005260:Female; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress
chemical_list: D001057:Apolipoproteins E; D004720:Endonucleases; D045647:DNA Glycosylases