| Abstract: | Tumor promotion associated with increased dietary fat may be inhibited by reduction in total caloric intake. This hypothesis was tested in rats given either 7,12-dimethylbenz(a)anthracene to induce mammary tumors or 1,2-dimethylhydrazine to induce colon tumors. One week after dosage with either carcinogen, the rats were fed semipurified diets that provided 4% fat with ad libitum calories or 13.1% fat with a reduction of calories by 40% from ad libitum intake. Rats treated with 7,12-dimethylbenz(a)anthracene and subjected to caloric restriction weighed 40% less than those fed ad libitum; rats treated with 1,2-dimethylhydrazine were heavier at the onset of caloric restriction and lost weight and weighed approximately 40% less than animals fed ad libitum. At 20 weeks after 7,12-dimethylbenz(a)anthracene administration, rats fed ad libitum had 80% tumor incidence while in those fed restricted calories, 20% had tumors (P less than 0.001). All other measures of mammary tumor growth were significantly reduced in rats given restricted calories. Six months after 1,2-dimethylhydrazine administration, colon tumor incidence was 100% in rats fed ad libitum and 53% in those fed the calorie-restricted diet (P less than 0.001). This reduction of colonic carcinogenesis was seen despite a significant increase in mucosal labeling index following 3H]thymidine autoradiography. This paradoxical finding may be due to the increased fat content of the calorie-restricted diet. These data demonstrate that the tumor-promoting effects of dietary fat can be more than offset by a reduction in total caloric intake and that the promoting effect of fat may be due, at least in part, to its greater caloric density. |
