Effect of duration of high fat intake on enhancement of mammary carcinogenesis in rats.

The relationship between dietary fat and mammary carcinogenesis was studied in weanling female inbred Fischer rats fed a purified, high-fat, low-carbohydrate (HF) or a purified, low-fat, high-carbohydrate (LF) diet and given N-nitroso-N-methylurea (NMU) at 50, 90, or 133 days of age. By a change in the diet at different times after NMU treatment (50 mg/kg body wt), it was found that mammary tumor incidence was positively correlated with the time period that the rats were fed an HF diet. A dose-response effect of NMU at 10, 20, 30, 40, and 50 mg/kg body weight was also studied in groups of rats fed an HF or an LF diet. The results show an optimal carcinogenic dose of 50 mg NMU/kg body weight and a threshold dose of 27 mg NMU/kg body weight. The data conclusively demonstrated that the HF diet enhanced mammary carcinogenesis at every dose level of NMU, except 10 mg/kg. Further, the experiments also showed that an HF diet failed to promote mammary carcinogenesis in rats receiving a subthreshold dose (20 mg/kg body wt) of NMU. Altogether, the data demonstrate that an HF diet is not just a promoter but is in fact co-carcinogenic in mammary tumor induction by a chemical carcinogen.