Dietary lipids and calorie restriction affect mammary tumor incidence and gene expression in mouse mammary tumor virus/v-Ha-ras transgenic mice

• Published in: Proceedings of the National Academy of Sciences - PNAS 1995-07, Vol.92 (14), p.6494-6498
• Main Authors: Fernandes, G. (University of Texas Health Science Center, San Antonio, TX.), Chandrasekar, B, Troyer, D.A, Venkatraman, J.T, Good, R.A
• Format: Article
• Language: English
• Subjects: ACEITE DE MAIZ; ACEITES DE PESCADO; ANIMAL TRANSGENIQUE; ANIMALES TRANSGENICOS; Animals; ARN MENSAJERO; ARN MESSAGER; Blotting, Northern; Blotting, Southern; Breast cancer; Breast neoplasms; Calories; CARCINOGENOS; CATALASA; CATALASE; Catalase - biosynthesis; Corn Oil; Death; Diet; Diet, Reducing; DIETA; DIETA TERAPEUTICA; Dietary Fats; DNA, Neoplasm - analysis; Energy Intake; ENFERMEDADES GLANDULAS MAMARIAS; Enzymes; Female; Fish Oils; FOIE; GENE; Gene Expression; GENES; Genes, ras; Glutathione Peroxidase - biosynthesis; Glyceraldehyde-3-Phosphate Dehydrogenases - biosynthesis; HIGADO; HUILE DE MAIS; HUILE DE POISSON; Humans; INANICION; INANITION; Incidence; Interleukin-6 - biosynthesis; Lipids; MALADIE DES GLANDES MAMMAIRES; Mammary Neoplasms, Experimental - epidemiology; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Mammary Neoplasms, Experimental - prevention & control; Mammary Tumor Virus, Mouse - genetics; Medical research; Messenger RNA; Mice; Mice, Transgenic; NEOPLASMAS; NEOPLASME; Oils & fats; RATON; Receptor, ErbB-2 - biosynthesis; REGIME ALIMENTAIRE; REGIME ALIMENTAIRE THERAPEUTIQUE; RETROVIRIDAE; RNA; RNA, Messenger - analysis; RNA, Messenger - biosynthesis; RNA, Neoplasm - analysis; Rodents; SOURIS; SUBSTANCE CANCERIGENE; Superoxide Dismutase - biosynthesis; SUPEROXIDO DISMUTASA; SUPEROXYDE DISMUTASE; SUPERVIVENCIA; SURVIE; TRANSFERASAS; TRANSFERASE; Transgenes; Tumors; VALEUR CALORIQUE; VALOR CALORICO; VIRUS
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.14.6494

We have studied the effects of food restriction (FR) and substitution of fish oil (FO; omega 3) for corn oil (CO; omega 6) on breast tumor incidence and survival in mouse mammary tumor virus/v-Ha-ras transgenic (Onco) mice. The diets were as follows: group 1, 5% (wt/wt) CO fed ad libitum (AL); group 2, 5% CO, restricted calories (40% fewer calories than AL; FR); group 3, 20% CO fed AL; and group 4, 20% FO fed AL. After 3 years, 40% of FR Onco (group 2) mice were alive, whereas there were no survivors in the other three groups. Similarly, tumor incidence was reduced to 27% (5 out of 18) in FR animals (group 2), whereas it was 83% (11 out of 13) in group 1 mice, 89% (16 out of 18) in group 3 mice, and 71% (10 out of 14) in group 4 mice. These protective effects of FR on survival and tumor incidence were paralleled by higher expression of the tumor suppressor gene p53 (wild type) and free-radical scavenging enzymes (catalase and superoxide dismutase) in breast tumors. Immunoblotting showed less ras gene product, p21, and increased p53 levels in the tumors of FR mice. In addition, FR decreased RNA levels of c-erbB-2, interleukin 6, and the transgene v-Ha-ras in tumors. In contrast, analysis of hepatic mRNA from tumor-bearing FR mice revealed higher expression of catalase, glutathione peroxidase, and superoxide dismutase. Survival and tumor incidence were not influenced significantly by dietary supplementation with FO in place of CO. Taken together, our studies suggest that moderate restriction of energy intake significantly inhibited the development of mammary tumors and altered expression of cytokines, oncogenes, and free-radical scavenging enzymes