Effect of dietary fat on growth of MCF-7 and MDA-MB231 human breast carcinomas in athymic nude mice: relationship between carcinoma growth and lipid peroxidation product levels
Human breast carcinoma cell lines MCF-7 and MDA-MB231 were transplanted s.c. to female athymic nude mice at 3–4 weeks of age. At 7–10 days after transplantation, the mice were divided into groups and fed for 6–8 weeks one of the following semi-purified diets containing different amounts and types of fat, i.e. 5% corn oil, 20% corn oil, 20% butter, 19% beef tallow/1% corn oil and 19% fish (Menhaden) oil/1% corn oil. In additional experiments, the fish oil diets were supplemented with antioxidants (vitamin E, 8 g or 2000 IU/kg diet plus tertiary butyl hydroqulnone, TBHQ, 4 g/kg diet) or ferric citrate (3 g/kg diet). Tumor peroxidation product levels were assessed by measuring 2-thiobarbituric acid reactants (TBA assay). At the tennination of the studies (6–8 weeks of diet feeding) mean human breast carcinoma volume (MCF-7 and MDA-MB231) was the largest in mice fed the 20% corn oil diet, intennedlate in mice fed the butter or beef tallow diets and the least in mice fed the fish oil diet. The difference in mean tumor volumes among mice fed the 20% corn oil diet and those fed the fish oil diet was significant (P < 0.01). When comparing low (5% corn oil) and high (20% corn oil) fat diets, numerical increases in human breast carcinoma volume (MCF-7 and MDA-MB231) were consistently observed in the high-fat diet groups but these differences were not always significant. Tumor lipid peroxidatlon product levels were determined on the MDA MB231 tumors; tumor lipid peroxidation levels were significantly (P < 0.01) increased only in mice fed the fish oil diets. Supplementation of the fish oil diets with antioxidants (vitamin E + TBHQ) significantly reduced the level of tumor peroxidatlon products and significantly increased tumor volume (P < 0.05). When tumor lipid peroxidation product levels in the fish oil plus antioxidant fed mice were reduced to the level of that observed in the tumors of the corn oil fed mice, no significant differences in tumor volumes were observed in these two groups. In contrast, supplementation of the fish oil diets with ferric citrate, significantly (P < 0.05) increased tumor lipid peroxidation product levels and decreased tumor volume. Thus, the type of dietary fat can clearly aftect the growth of human breast carcinomas (MCF-7 and MDA-MB231) maintained in athymic nude mice. The consistent and significant inhibition of dietary fish oil (Menhaden) on growth of these carcinomas appears to be due to an increased accumulation of tumor lipid peroxidation products.