Dietary fat versus caloric content in initiation and promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats

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-dimethyl-benz(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, high-calorie 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.