1957 Volume 10 Issue 3 Pages 120-127
During the course of the search for new antibiotics produced by streptomyces, the culture filtrate of a new isolated streptomyces, Str. caespitosus, active against gram-positive and gram-negative bacteria, was found also to exert a destructive action upon the cells on experimental malignant tumors. The effective principles were isolated and fractionated into mitomycin A and mitomycin B, of which the physico-chemical properties have been described in a previous paper1). Mitomycin C was isolated shortly thereafter. All of them possess, in common antibacterial and antitumor activities, though their physico-chemical properties are different.
Experiments were then conducted to determine their effects upon the malignant tumors, Ehrlich carcinomaand Yoshida sarcoma. Mitomycins A and C were employed as they were available insufficient quantity at that time.
In the screening experiments of antitumor activity, the supension of Ehrlich carcinoma cells was transplanted intraperitoneally to mice. This was followed after 24 hours by the intraperitoneal injection of 0.2–0.5ml of the culture filtrate. The ascitic fluid was taken 16–18 hours after the injection, and the number of tumor cells in the ascitic fluid was counted2). In contrast to 70–90% of tumor cells in the smeared specimen from control animals, the proportion of tumor cells in cellular elements in the ascitic fluid from the mice, which had received the injection of the culture filtrate decreased to about 10%. In addition, this culture filtrate showed some ability to prolong the survival time of mice inoculated with Ehrlich carcinoma. These results suggested the existence of tumor-inhibitory substances in the culture filtrate of Str. caespitosus.
The tumor-inhibitory activity of the culture filtrate was proved to be in good correlation with its activity against Bacillus subtilis PCI 219. Experiments on fermentation and extraction of mitomycins, based upon this relationship, have been performed as described in the previous paper1).
Wide differences exist in the antibacterial activity and acute toxicity between each fraction of the culture filtrate of crude preparation of mitomycin obtained in the earlier stage of extraction. Therefore the experiments were performed with each fraction and the results are described in this paper.