The Effects of Sex Hormones on the Induction of Mammary Carcinomas in Male Rats by Pulse Doses of 7,12-Dimethylbenz(a) anthracene.

Abstract

Male Sprague-Dawley rats were orally dosed with 10 mg 7, 12-dimethylbenz(a)anthracene 3 or 5 times at 14-day intervals starting from 28 days of age. The male rats were treated with various hormonal treatments such as castration and/or injections (3 times/week) of various doses of 17β-estradiol or progesterone, 14 days after the last administration of 7, 12-dimethylbenz(a)anthracene. Extreme secretion in the wide lumina of the acini of the mammary glands was observed in rats given injections at high doses (0.1 mg and 1 mg) of 17β-estradiol. However, there was little lumina of acini without secretion in developed mammary glands in rats given injections of progesterone. This feature of the mammary glands suggests increased levels of progesterone and estrogens in rats given injections of progesterone because of the conversion of progesterone to estrogen. Number of rats with carcinoma and number of carcinoma per rat increased extremely and slightly in rats given injections of 0.01 mg 17β-estradiol or injections of 4 mg progesterone and in rats given injections of high doses (0.1 mg and 1 mg) of 17β-estradiol, respectively. These results indicate that suitable doses of estrogen, particularly 0.01 mg 17β-estradiol promote the progression of male mammary carcinogenesis. In rats given injections of high doses (0.1 mg and 1 mg) of 17β-estradiol, the number of carcinomas with squamous metaplasia increased significantly, and the number of estrogen receptor-positive carcinomas decreased extremely when cells with nuclei stained by immunohistochemical methods were interpreted as positive cells, and a tumor with 20% of positive cells was considered estrogen receptor-positive.