Xanthocidin, a new antibiotic, has been obtained from Streptomycete isolated from a soil sample collected at Rikugo-machi, Yamanashi Prefecture. This report will describe the organism, medium employed for the production of xanthocidin, the isolation procedure, and some of the physical, chemical and biological properties of the antibiotic.
Phleomycin described by Maeda et al. 1), Takita et al.2) and Takita3), is produced by Streptomyces verticillus and is obtained as a blue powder containing copper. The copper can be removed by treatment with 8-hydroxyquinoline and the copper-free phleomycin is also biologically active. Later, this antibiotic was found by Lein et al4) to cause the induction of lysogenic bacteria and was found by Bradner et al.5) and Umezawa et al.6) to exhibit inhibition of experimental tumors in mice and rats. As recorded by Tanaka et al. 7), it inhibits DNA synthesis but does not cause breakdown of DNA. The selective inhibition of DNA polymerase reaction was reported by Falaschi and Kornberg8). As reported by Ikekawa et al. 9), phleomycin can be separated by the ion gradient chromatography on CM-Sephadex C-25 into components such as A, B, C, D1, D2, E, F, G1, G2, H, I, all of which chelate with copper, show similar ultraviolet spectra, and have similar biological activities. As reported in another paper by Ishizuka, Takeuchi and Umezawa10), in dogs phleomycin causes kidney damage which seems to be irreversible. Phleomycin has basic property and therefore we suspected that the kidney toxicity and the antitumor activity might be dependent on different modes of action. Therefore, we tried to find other antibiotics which were resembling to phleomycin but could be differentiated from the latter. Searching new strains of Actinomycetes isolated from soils, we found that a group of antibiotics produced by a strain of Streptomyces verticillus newly isolated were differentiated from phleomycins in the stability and Rf values on paper chromatograms. The group of the antibiotics produced by this strain was named bleomycin. Bleomycin was separated into A and B. A and B are differentiated by Rf values on paper chromatograms. As described in another paper by Ishizuka, Takeuchi and Umezawa11), when bleomycin complex consisting mainly of A was injected in dogs, the toxicity appeared in the hardening of skin of feet pad and in the reduction of liver function, which were recovered by the cessation of the administration of bleomycins. This complex showed a high therapeutic index against Ehrlich carcinoma and sarcoma 180 in mice.
Bleomycins have been briefly reported by Umezawa et al. 12) and in this paper, the isolation and the characterization of bleomycin A and B are presented.
Among antibiotics inhibiting Trichophyton produced by Actinomycetes, those which did not show the polyene character were selected and one of them was determined to be a new antibiotic and named spinamycin. The properties of the strain producing this antibiotic, the isolation and the character of spinamycin are presented in this paper.
According to the reports by Rajam1) and Pital et al. 2) the oxidation-reduction dyes such as triphenyltetrazolium chloride (T.T.C.) and resazurin were attempted to be available for the rapid determination of sensitivities of bacterice to chemotherapeutics, because the dyes could be reduced to change their colors by the respiration of living organisms.
We also reported3) that the use of commercially available sensitivity disc in the rapid determination with T.T.C. or 2,6-dichlorophenolindophenol as indicator could make the procedure more simple and that resazurin was most useful in comparison with T.T.C., neotetrazolium chloride and 2,6-dichlorophenolindophenol, because of higher sensitivity and less inhibitory activity to the growth of microorganisms.
Brown et al.5) and Rieringer et al.6)reported the rapid determination of drug-sensitivities by using paper discs which had been impregnated with T.T.C., chemotherapeutics and medium.
In this paper we describe a rapid determination method for sensitivity by adding the liquid medium inoculated with organisms to be tested to the discs which had been prepared to contain resazurin and chemotherapeutics.