Inhibition of Chemically Induced Mammary and Colon Tumor Promotion by Caloric Restriction in Rats Fed Increased Dietary Fat1

Tumor promotion associated with increased dietary fat may be inhib ited by reduction in total caloric intake. This hypothesis was tested in rats given either 7,12-dimethylbenz(fl)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 7,12dimetliylben/.(«)anthracene and subjected to caloric restriction weighed 40% less than those fed ad libitum; rats treated with 1,2-dimethylhydra zine 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(<i)anthracene administration, rats fed ad libitum had 80% tumor incidence while in those fed restricted calories, 20% had tumors (/' < 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 inci dence was 100% in rats fed ad libitum and 53% in those fed the calorierestricted diet (P < 0.001). This reduction of colonie carcinogenesis was seen despite a significant increase in mucosa! labeling index following |MIjthymidine autoradiography. This paradoxical finding may be due to the increased fat content of the calorie-restricted diet. These data dem onstrate 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.