Mutagenesis Advance Access originally published online on January 18, 2007
Mutagenesis 2007 22(2):105-110; doi:10.1093/mutage/gel059
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Oxidatively damaged DNA in aging dyslipidemic ApoE–/– and wild-type mice
Department of Occupational and Environmental Health, Institute of Public Health, University of Copenhagen, Øster Farimagsgade 5, building 5, 2nd floor, 1014 Copenhagen K, Denmark
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 (
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.
* To whom correspondence should be addressed. Tel: +45 3532 7654; Fax: +45 3532 7686; Email: p.moller{at}pubhealth.ku.dk
Received on August 25, 2006; revised on October 24, 2006; accepted on October 31, 2006.