Inhibition of DMBA-Induced Mammary Carcinogenesis in the Rat by 2-Br-α-Ergocryptine (CB 154), An Inhibitor of Prolactin Secretion, and by Nafoxidine (U-11, 100 A), an Estrogen Antagonist
The DMBA-induced mammary carcinogenesis in the Sprague-Dawley rat is known to be both estrogen and prolactin dependent. The experiments presented here show that 2-Br-Α-ergocryptine (CB 154), an inhibitor of prolactin secretion, and nafoxidine (, 100 A), an estrogen antagonist, inhibit the U 11 successive stages of carcinogenesis, namely formation of preneo plastic nodules, transformation of the latter into tumors, and finally growth of the established tumors. Endocrine studies, involving histological examination of organs and serum prolactin determination by radioimmunoassay, show that CB 154 inhibits prolactin secretion and produces peripheral changes consistent with this effect, and that nafoxidine behaves as an antiestrogen in intact animals and in oophorectomized animals given estrogens, that it is devoid of intrinsic estrogenic properties but rather displays progestational-like effects, and that it inhibits prolactin stimulation by estrogens in oophorectomized rats. The antitumor effect of CB 154 can be ascribed to interference with prolactin secretion. That of nafoxidine may result from its antiestrogenic properties at the tumor tissue level, although part of it could be tentatively ascribed to inhibition of prolactin secretion.