Effect of Duration of High Fat Intake on Enhancement of Mammary Carcinogenesis in Rats23

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Abstract
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.

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