Effect of 3-methylcholanthrene on the development of aortic lesions in mice

The effect of a carcinogen, 3-methylcholanthrene (3-MC), on the formation and growth of atherosclerotic lesions in mice was examined. Increasing doses of 3-MC from 15 to 1500 micrograms/kg increased the number and size of lipid-staining lesions in the aorta of AKXL-38a mice that were fed an atherogenic diet for 8 weeks. The number of lesions per mouse was 0.85 +/- 0.19 (SE) for animals treated with 3-MC (150 micrograms/kg) compared to 0.10 +/- 0.10 lesions/mouse for animals given solvent rather than 3-MC. The progression of lesions over time from 5 to 18 weeks showed that 3-MC-treated mice also differed from controls in the size of lesions. The total score per mouse at 18 weeks of atherogenic diet, based on the number of lesions and the size of each lesion, indicated by a score of 1 to 4, was 4.31 +/- 0.71 for 3-MC-treated animals and 2.67 +/- 0.74 for animals given solvent. The effect of 3-MC treatment could be observed at 18 weeks even though the entire dose of 3-MC was given during the first week on the atherogenic diet. These experiments do not distinguish whether 3-MC affects atherosclerotic lesions by acting as a mutagen or by some other mechanism. The composition of an atherogenic diet that produces lesions in mice without high mortality is given as well as a comparison of different methods of evaluating lesion formation.