Antibiotics which inhibit both Gram positive and negative bacteria and which are extracted by the process used for the extraction of streptomycin or streptothricin, that is, by the adsorption to carbon and the elution into acid methanol or by the cation exchange resin process, are produced by various species of actinomycetes. Some of them such as streptomycin and fradiomycin (neomycin)1~2) have no delayed toxicity, but many others have delayed toxicity. In the systematic screening studies made by the authors, antibiotics showing the delayed toxicity were discarded and those without the delayed toxicity were further studied and purified. Thus, kanamycin was discovered and presented in this paper.
Here it seems to be worthy to note an antibiotic produced by S. roseochromogenus, though it has no relation with kanamycin. Ishida3) first described that he isolated a low toxic antibiotic from the culture liquid of S. roseochromogenus. The authors also obtained a similar substance from another strain belonging to the same species. At the beginning of the study, the antibiotic of this strain did not show the delayed toxicity, but, when the productivity of the strain was improved and the antibiotic was further purified, then the antibiotic showed the delayed toxicity similar to streptothricin. Thereafter, the author failed to isolate the low toxic antibiotic from this strain. In case of kanainycin, the kanamycin-producing strain is clearly different from S. roseochromogenus and the low toxic kanamycin is constantly isolated.
Kanamycin shows dextrorotation, but it is differentiated from the dextrorotatory antibiotics such as fradiomycins (neomycins), catenulin, and geomycin, and it is a new antibiotic.
In this paper the characteristics of the kanamycin-producing strain, the production, the extraction and the purification are presented.
As shown by the antibiotic studies, microorganirms are rich sources of chemical compounds, and from the viewpoint of the present situation of cancer chemotherapy it is reasonable to search new antitumor substances in microbial products. Such antibiotics as actinomycins C and D1), puromycin2), sarkomycin3), azaserine4), carzinophilin5), actinoleukin6), mitomycin7), carcinomycin8), pluramycin9), gancidin10), 6-diazo-5-oxo-norleucine11), toyokamycin, hygroscopin, fumigillin and melanomycin7) have been reported to retard growth of transplantable neoplasms in animals. A trial of finding more effective and less toxic antitumor substances is continued in this laboratory. Since 1955, approximately 1300 soil actinomycetes have been studied for their formation of metabolic products suppressing growth of transplantable animal tumors. Crude filtrates from cultures of actinomycetes each in 0.3ml daily were intraperitoneally injected into mice bearing Ehrlich carcinoma of ascitic form or Crocker sarcoma 180 of the same form for 8 days since the day of inoculation of tumor cells. In the repeated animal experiments it was confirmed that by the method employed approximately 2% of soil actinomycetes produced antitumor substances, which prolonged the survival period as well as retarded the ascites increase. Of these antitumor agents, raromycin produced by strain No. 314 C1 was studied in detail because of its low toxicity and its high effectiveness against both animal tumors.
The present paper describes the studies on the effect of the crude powder of raromycin on Ehrlich carcinoma and Crocker sarcoma 180; both solid and ascitic forms in mice. Detailed chemical and biological studies of this agent will be reported in other papers.
In the studies searching new antibiotics inhibitory against Gram negative bacteria, an antibiotic containing sulfur was found by the authors and was named althiomycin. This white crystalline antibiotic inhibits growth of both Gram positive and negative bacteria, but not that of fungi.
It is relatively low toxic and it exhibited protective effect against infection of the sensitive organisms.
The present paper describes characters of the althiomycin-producing strain, processes for the production and the isolation, and properties of the antibiotic.
In the course of searching new antibiotics active against tubercle bacilli, a new antibiotic, named tubercidin, was obtained in the crystalline form from the broth of an unidentified actinomyces strain which was isolated from the soil of Chiba Prefecture. This antibiotic also showed a strong antitumor action in vitro, using NF mouse sarcoma. The present paper deals with its isolation, purification and physical and chemical properties as well as its biological activity.
A yellow crystalline antibiotic with weakly acidic properties has been isolated from the culture broth of a new species of Streptomyces. This organism, indexed S-66 in our culture collection, has been isolated from a soil sample collected from Aburabi, Shiga Prefecture. The antibiotic, which we have named aburamycin, is active against gram-positive organisms and, moreover, it shows some inhibitory effect on Ehrlich ascites tumor and Crocker sarcoma in mice.
The purpose of the presnt paper is to describe the antibiotic-producing organism and to report preliminary studies on production, isolation, antimicrobial spectrum, anti-tumor activities and properties of aburamycin.
In the previous paper(1), the author reported antitumor effect of actinomycin J on Ehrlich carcinoma, mouse sarcoma 180 and Yoshida rat sarcoma. Actinomycin J and pluramycin A, both have strong antibacterial activities and they are reddish pigments of streptomyces. According to a report of Umezawa and others(2,3) pluramycin A exhibited antitumor activity on Ehrlich carcinoma much stronger than that of actinomycin J. Comparative studies on antitumor effects of these antibiotics made by the same researcher was considered to be helpful for the evaluation of their antitumor activities. This report describes results of experiments testing antitumor effects of pluramycin A on three kinds of experimental animal tumors described above.
The quantitative analysis of streptomycin resistance in bacterial population occurring in the sputum was made by only a few investigators (Pyle1), Kozokai2), Mitchson3)). However, there is none of the quantitative studies concerning the change of population with respect to streptomycin resistance after cessation of streptomycin administration. It is known by routine method studies that streptomycin resistance is persistant (Fisher4)). The purpose of the present study is to test whether the bacterial population in sputum is permanently maintained and to observe the relationship between streptomycin resistance developed by streptomycin therapy at first made and the therapeutic effect of chemotherapy with isoniazid and PAS (isoniazid-PAS therapy) followingly made.