Ability of Dietary Fat to Overcome the Resistance of Mature Female Rats to 7,12-Dimethylbenz(a)anthracene-induced Mammary Tumorigenesis¹

The present study is designed to delineate the action of dietary fat on the development of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary tumors in female Sprague-Dawley rats and to investigate the interdependence of fat intake and age as modifiers of mammary oncogenesis. Compared to rats given DMBA at 50 days of age (immature rats), rats that were exposed to DMBA at 150 days of age (mature rats) were more resistant to the carcinogen irrespective of fat intake, although the incidence of tumors in rats fed a high-fat diet (20% corn oil) still remained substantially higher than in those rats on a low-fat diet (0.5% corn oil) at different doses of DMBA tested. In this experiment, both diets were fed from weaning until termination of the experiment. When adult rats (150 days old) were given 5 mg of DMBA each week for 4 consecutive weeks, tumors appeared earlier, and the proportion of adenocarcinomas to fibroadenomas was higher in the group that was fed the 20% fat diet. Using the adult rats as the model for tumor induction, the contribution of a high dietary fat intake before and after DMBA administration in the promotion of mammary tumorigenesis was assessed. The types of diet fed before and after DMBA were designated LF-LF, LF-HF, HF-LF, and HF-HF, in which LF and HF represent 0.5% and 20% fat diets, respectively. Results of this experiment established the following order of tumor incidence: HF-HF (84.0%) > LF-HF (60.9%) > HF-LF (36.0%) > LF-LF (20.8%). It appears from this study that the level of fat intake after DMBA treatment is more important in determining the subsequent development of mammary cancer than is fat intake prior to DMBA administration, thus confirming earlier observations reported by Carroll and Khor and by Hopkins, Hard, and West. In addition, it was also found that in rats that were fed a 0.5% fat diet from weaning and given a single dose of 5 mg of DMBA at 50 days of age, a transfer to a 20% fat diet as late as 20 weeks after DMBA was able to stimulate a significant increase in the number of rats bearing tumors. It can be concluded from these findings that dietary fat acts preferentially, although by no means exclusively, on the promotional phase of carcinogenesis and that the differential effect of high-fat and low-fat diets on tumorigenesis can be demonstrated regardless of the age at which the carcinogen is given.