Effect of Dietary Fat, Antiestrogen, and Antiprolactin on the Development of Mammary Tumors in Rats2

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Abstract
After a single oral dose of 5 or 10 mg 7, 12-dimethylbenz[a]anthracene (DMBA), female Sprague-Dawley rats fed a high fat (HF) semisynthetic diet developed mammary tumors earlier and in greater numbers than rats fed a low fat (LF) diet. The average growth rate, based on body weight, was comparable in both groups. To determine whether the dietary effect might be mediated by changes in hormones such as estrogen and prolactin, DMBA-pretreated rats fed HF and LF diets were given the antiprolactin drug CB-154 or the antiestrogen drug U11,100A and breast tumor incidence was measured. Whereas breast tumor development was decreased in extent and speed by the antiestrogen, the differential incidence of tumors in rats fed an HF diet remained higher in comparison to rats on an LF diet. In contrast, the antiprolactin drug completely suppressed the formation of all palpable mammary tumors at a DMBA dose of 5 mg in rats on either LF or HF diets. At a dosage level of 10 mg DMBA, not only was the tumor incidence decreased by the antiprolactin drug but the differential effect of dietary fat was abolished. By inference, the data from this study suggest that enhancement of mammary tumor growth, induced by high dietary fat, may be med iated through alterations in circulating levels of prolactin.

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