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Effects of Dietary Protein, Fat and Energy Intake during an Initiation Phase Study of 7,12-Dimethylbenz[a]anthracene-Induced Breast Cancer in Rats^1,2,

Steven K. Clinton^3,*, Joan M. Alster, Peter B. Imrey, Steven Nandkumar, C. Richard Truex^* and Willard J. Visek^4,*

^* Nutrition and Metabolism Medical Statistics and Epidemiology Pathology, University of Illinois College of Medicine, Urbana, IL 61801

A factorial experiment was conducted to examine the effects of dietary protein (8, 16, 32% of energy from casein) and dietary fat (12, 24, 48% of energy from corn oil) on the initiation of 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast carcinogenesis in rats. Forty weanling female Sprague-Dawley rats were assigned to each of nine diets fed ad libitum. After 4 wk each rat received DMBA (20 mg/kg) via gastric intubation. For an additional 22 wk after carcinogen administration all rats consumed a diet containing 16% of dietary energy from protein and 24% from fat. Dietary fat, protein and ad libitum energy consumption exhibited statistically significant effects on final tumor prevalence, but interactive effects were not found. At necropsy, rats fed corn oil at 12, 24 and 48% of energy prior to DMBA administration showed tumor prevalences of 58, 58 and 85% with 116, 153 and 231 total tumors, respectively. The data indicate a significant nonlinear effect of dietary fat. Corresponding numbers for rats fed casein at 8, 16 and 32% of energy prior to DMBA were prevalences of 79, 65 and 59%, with total tumor counts of 194, 144 and 162. Higher dietary protein during the initiation phase was associated with a significant reduction in tumor prevalence, which was most striking between 8 and 16% of energy from protein. In addition, results of multiple logistic regression showed that tumorigenesis was increased with greater ad libitum energy intake. The odds of a tumor at necropsy were multiplied by 1.19 for each kilocalorie increase in ad libitum energy intake averaged over the post-DMBA phase of the experiment. An additional six weanling rats fed each diet for 4 wk were killed for assay of hepatic carcinogen metabolizing enzymes at the time corresponding to DMBA administration in the initiation experiment. Both protein and fat showed independent effects on the activity of several enzymes. However, enzyme activity did not suggest a unifying mechanism whereby these nutrients influence DMBA-induced mammary carcinogenesis.

KEY WORDS: • dietary fat • corn oil • dietary protein • casein • caloric intake • 7,12-dimethylbenz[a]anthracene • breast cancer • rats

¹ This research was supported by National Cancer Institute of the National Institutes of Health Grant Nos. CA29629 and CA23326 and Environmental Toxicology Training Grant No. USPHS-ES 070001-17.

² A preliminary report of this research was presented at the 65th Annual Meeting of the Federation of American Societies for Experimental Biology, Atlanta, GA, April 1981. Clinton, S. K., Truex, C. R., Nandkumar, S., Imrey, P. B. & Visek, W. J. (1981) Dietary protein-fat interactions in the initiation and promotion of 7,12-dimenthylbenz[a]anthracene (DMBA) mammary cancer. Fed. Proc. 40:948 (abst. 4071).

³ Present address: The University of Chicago, Department of Medicine, 950 East 59th Street, Chicago, IL 60637.

⁴ To whom requests for reprints should be addressed.

Manuscript received 18 February 1986. Revision accepted 16 June 1986.