Effect of Enol-Ether Derivatives of Dihydrotestosterone on 3-Met hylcholanthrene-Induced Rat Mammary Carcinoma

Abstract

A series of enol ethers of dihydrotestosterone, described for the first time and showing low androgenic activity, was tested against hormone-dependent adenocarcinomas that had been induced in Sprague-Dawley rats by oral administration of 3-methylcholanthrene (3-MCA). Two types of tests were conducted: The prevention test was designed to determine whether the enol ethers of dihydrotestosterone, given intramuscularly for 50 days, are effective in delaying the average time of the appearance of tumors induced by 10 mg of 3-MCA. This was administered orally and simultaneously with the steroid. The regression test evaluated the diminutive effect of the enol ethers, given intramuscularly for 30 days, on mammary cancers induced by 3-MCA. The prevention test showed that most of the enol ethers of dihydrotestosterone efficiently reduced the incidence and delayed the appearance of mammary cancers. In the regression test some of the enol ethers diminished the tumor size to a degree equal to, or even greater than, that observed after ovariectomy or the application of dihydrotestosterone. The regressions were histologically consistent with atrophy of epithelium and sclerosis. The maximal antitumor effect was displayed by dihydrotestosterone enol ethers with an alcohol moiety of 8 or 12 carbon atoms.