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The Combined Effects of Dietary Protein and Fat Intake during the Promotion Phase of 7,12-Dimethylbenz(a)anthracene-Induced Breast Cancer in Rats¹

Steven K. Clinton^*,2, Joan M. Alster, Peter B. Imrey, Joseph Simon and Willard J. Visek^*,3

^* Division of Nutritional Sciences, Department of Internal Medicine Medical Statistics and Epidemiology Section, Department of Medical Information Science, College of Medicine Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana, Illinois 61801

A 3 x 3 factorial experiment was conducted to examine the effects of dietary protein (8, 16 or 32% of energy from casein) and dietary fat (12, 24 or 48% of energy from corn oil) on the promotion phase of 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis in rats. A purified diet with protein and fat supplying 16 and 24% of energy, respectively, was fed to 360 rats. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. Forty rats were then randomly assigned to each of the nine dietary treatments for 28 wk. We observed no effects of protein or interactions between protein and fat on mammary tumorigenesis. At necropsy, rats fed diets containing 12, 24 and 48% of energy from corn oil following DMBA administration showed tumor prevalences of 53, 60 and 70% with 109, 127 and 140 total tumors, respectively. Linear logistic statistical modeling indicated that each doubling of dietary fat concentration multiplied the odds of finding a tumor of any histologic type at necropsy by 1.52. Dietary fat had no significant effects on the prevalence of adenomas or fibroadenomas, whereas those fed corn oil at 12, 24 and 48% of dietary energy showed adenocarcinoma prevalences of 34, 41 and 52% with total adenocarcinoma counts of 66, 75 and 96, respectively. Our results suggest that increasing dietary fat enhanced the promotion of DMBA-induced breast carcinogenesis over a wide range of protein intake.

KEY WORDS: • dietary fat • corn oil • dietary protein • casein • 7,12-dimethylbenz(a)anthracene • breast cancer • rats

¹ This research was supported by the Public Health Service, National Institutes of Health, National Cancer Institute, Grant Nos. CA 23326, CA 29629, and Environmental Toxicology Training Grant No. USPHS-ES 070001-17.

² Present address: Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115.

³ To whom requests for reprints should be addressed.

Manuscript received 10 March 1988. Revision accepted 23 June 1988.