The Concurrence of Hypercholesterolemia and Aging Promotes DNA Damage in Apolipoprotein E-Deficient Mice

Recent evidence shows that increased oxidative stress and aging contribute to DNA damage in various cardiovascular diseases such as lipid disorders and atherosclerosis. In the present study, we used the comet assay to evaluate the influ- ence of aging on DNA damage in whole blood cells from apolipoprotein E-deficient (apoE?/?) mice and compared the results to those found in cells from wild-type C57BL/6 (C57) mice. Using the alkaline comet assay and fluorescent ethidium bromide staining, DNA damage was analyzed in the peripheral whole blood (5 μL) cells that were isolated from either young (8-week-old) and elderly (72-week-old) apoE?/? mice or from age-matched C57 mice. The levels of total plasma cholesterol were approximately 6-fold higher in apoE?/? mice of both ages compared to C57 mice. Elderly apoE?/? mice showed significantly higher levels of DNA damage (19%) compared to elderly C57 mice (8%, p < 0.01) and young apoE?/? mice (10%, p < 0.01). The comet assay in whole blood cells is a suitable technique for the detection of DNA damage in the apoE?/? mouse; it is an easy, rapid, inexpensive and sensitive method. The novelty of this study is that DNA damage occurring in whole blood cells of this murine model requires the concurrence of aging and oxida- tive stress-related hypercholesterolemia.