Influence of dietary fat on the induction of mammary tumors by N-nitrosomethylurea: associated hormone changes and differences between Sprague-Dawley and F344 rats.

A single iv dose of N-nitrosomethylurea (NMU, 50 mg/kg) given to 50-day-old F344 and Sprague-Dawley rats was sufficient to induce mammary adenocarcinomas. The Sprague-Dawley rats were more sensitive to the carcinogenic action of NMU than were the F344 rats. Moreover, regardless of strain, tumors developed in greater numbers and with a shorter latent period in animals fed a high-fat (HF) diet compared with animals fed a low-fat (LF) diet. The tumor-enhancing effect of HF diet was not related to body weight, since the mean body weight of the rats on the two diets was similar. In addition, no correlation was found between body weight and tumor incidence in individual rats under either dietary regimen. Since the most pronounced difference in tumor incidence between groups fed HF and LF diets was exhibited by the F344 rats, hormone analyses were performed on this group. At termination of the experiment, prolactin levels in the group fed an HF diet were significantly higher than those in the group fed an LF diet. Total estrogen levels were also significantly higher in the group fed an HF diet, compared with the group fed an LF diet, but this difference was seen only at the metestrus-diestrus stage. Regardless of diet or estrous cycle, when animals with tumors were compared with those without tumors, the former exhibited higher prolactin-estrogen (P/E) ratios. The results suggested a relationship between the ingestion of high levels of dietary fat, a high P/E ratio, and increased mammary tumor incidence.