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Dietary Fat versus Caloric Content in Initiation and Promotion of 7,12-Dimethylbenz(a)anthracene-induced Mammary Tumorigenesis in Rats¹

The Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104

Enhancement of mammary tumor formation by dietary fat may be mediated via increased caloric intake. Three experiments were performed to study this relationship in 7,12-dimethylbenz(a)anthracene (DMBA)-treated female Sprague-Dawley rats: (a) high- or low-fat isocaloric diets were fed in a crossover design; (b) low-fat, high-calorie and high-fat, low-calorie diets were fed in a crossover design; (c) pair-fed rats were restricted to 60% of the calories of controls with ad libitum access to food beginning 10 days after DMBA administration. The pair-fed rats received daily 60% of calories, the same level of fiber, and 115% more fat than did rats fed ad libitum. Tumor yield but not tumor incidence was greater in rats fed high-fat rather than low-fat isocaloric diets prior to initiation of tumorigenesis. A low-fat, highcalorie diet led to more tumor incidence and yield than was associated with feeding of a high-fat, low-calorie diet. Caloric restriction (although with concomitant intake of more fat) led to complete inhibition of tumor formation. These results indicate that both high-fat and high-calorie diets exhibit cocarginogenic, not merely promotional, properties. Caloric intake may be a greater determinant than dietary fat of a tumor-enhancing regimen. Finally, restriction of caloric intake during promotion markedly suppresses tumor formation, despite the increased fat content of the restricted diet, suggesting a permissive role for calories in tumor formation. The possibility remains that alterations in levels of other dietary components could also have contributed to the observed effects.

¹ Supported in part by Grants from Mary L. Smith, the National Dairy Council, the National Livestock and Meat Board, a Research Career Award (HL-00734) from the NIH, and funds from the Commonwealth of Pennsylvania.

² To whom requests for reprints should be addressed.

Received 10/20/83. Accepted 4/17/84.

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