Activity of 4 Beta-Hydroxy-17 Alpha-Methyl-19-Nortestosterone on Experimental Tumors

Abstract

The antitumor activity of a new steroid: 4β-hydroxy-17α-methyl-19-nortestosterone (HMNT) was studied on some mouse and rat tumors. The drug administered subcutaneously at the dose of 300 mg/kg/day inhibited the growth of Ehrlich carcinoma (45.8%) and of the first-generation transplants of C3H mammary adenocarcinoma. At the dose of 120 mg/kg/day the inhibition observed on Walker carcinoma was about 28%. HMNT was ineffective on sarcoma 180 when given both subcutaneously or orally at the same dose of 300 mg/kg/day. HMNT caused a marked reduction of TPCV of Ehrlich ascites tumor (66%) and of ascites hepatoma AH 130 (42%), and a moderate TPCV reduction of O.G.G. ascites mieloma (37.8%). In addition HMNT had a marked inhibitory effect on the mitotic index of Ehrlich ascites carcinoma. Diuresis and urinary excretion of electrolytes were not affected by the administration of HMNT in rats bearing ascites hepatoma. HMNT was compared to testosterone, progesterone and some other steroids for their antitumor activity: the results obtained support the hypothesis that the substitutions at posizion 4 β and 17 α and the removal of the methyl 19 from testosterone increase the effectiveness of the steroid. The results obtained by HMNT suggest that the action of the drug is performed through the slowing of the processes necessary for cell division.