Daunomycin: A New Antibiotic with Antitumor Activity

Abstract

Daunomycin is a new antibiotic isolated from cultures of Streptomyces peucetius. For its physicochemical characteristics it may belong to the group of antibiotics described by Ollis and Sutherland (11). The toxico-pharmacologic studies of Daunomycin administered i.v. to mice and rats indicated an acute LD50 value of 15-20 mg/kg. In the rat daily intravenous administration of 1-1.25 mg/kg for 8-14 days was well tolerated. Daily intravenous injection of 2-2.5 mg/kg for 8 days caused a slight decrease in the number of R.B.C. and W.B.C., but no histological damage was found in duodenal mucosa, testicles and other parenchimas. Daunomycin caused a significant inibition of 10 out of 12 tumors tested. At a daily dose of 1 or 2 mg/kg it had a marked inhibitory effect on ascites tumors (Hepatoma AH 130, Walker carcinoma, Ehrlich carcinoma, sarcoma 180 and O.G.G. myeloma) and remarkably increased the average survival time of the tumor-bearing animals. The antibiotic strongly inhibited also the growth of solid tumors (Ehrlich carcinoma 41.1%, 180 sarcoma 42.2%, Walker carcinoma 66.1%, O.G.G. myeloma 70.8 - 85.2% and MC sarcoma 67.6%). Daunomycin decreased the mitotic index of the Ehrlich ascites tumor and induced mitotic damages of tumor cells.