86 



NATURE, FORMATION, AND ACTIVITIES 



experimental moniliasis has recently been 

 carried out by Kosunen ( 1 959) . 



Antitumor Activities of Antibiotics 



The ability of various antibiotics to sup- 

 press the development of neoplasms resulted 

 in the isolation of a large number of com- 

 pounds from cultures of actinomycetes that 

 possess such a property (Reilly, 1953). This 

 was brought out in Chapter 3. Sevcik (1959) 

 divided these compounds into four catego- 

 ries on the basis of their antibiotic and anti- 

 tumor spectra: 



1. Substances active upon tumors, as well 

 as upon bacteria. These include actinoxan- 

 thine, azaserine, 6-diazo-5-oxo-L-no-leucine 

 (DON), cellocidin, alazopeptin, netropsin, 

 carzinophilin, aburamycin, actinomycin, rac- 

 tinomycin, pluramycin, amicetin, gancidin, 

 actinoleukin, griseolutein, levomycin, sulfo- 

 cidin, puromycin, desertomycin, mitomycin, 

 and others. 



2. Substances active upon tumors and 

 upon only one group of bacteria, namely, 

 M. tuberculosis. These include toyocamycin 

 and tubercidin. 



3. Substances active upon tumors and 

 fungi, but not upon bacteria. Ihese include 

 cycloheximide, hygroscopin, and polyenes. 



4. Substances active only upon tumors. 

 These include melanomycin, carzinocidin, 

 carcinomycin, and sarkomycin. 



The above groups were further subdivided 

 on the basis of their solubility in water. 

 Sevcik found the third group, comprising 

 the polyene compounds, to lie the most 

 widely distributed in nature, although he 

 doubted their practical usefulness. The nu- 

 cleotide antibiotics (puromycin, amicetin, 

 and carzinophilin A) appeared to be most 

 promising because of their relatively low 

 toxicity. The cjuinone-type antibiotics (ac- 

 tinomycins, pluramycin, ractinomycin, ac- 

 tinoleukin, and levomycin) were highly toxic. 



Oda (1960) also summarized our i-ecent 

 knowledge of antitumor antibiotics. Differ- 



ent experimental tumors in animals are used 

 for sci^eening purposes, such as Yoshida 

 sarcoma, Ehrlich carcinoma, mouse leu- 

 kemia, and others in Japan; sarcoma 180, 

 carcinoma 755, and mouse leukemia in the 

 United States. Oda emphasized that "the 

 present situation of antitumor antibiotic 

 research seems to l^e in the night l:)efore the 

 discovery of streptomycin and the author 

 wishes to hei'e introduce an outline of I'e- 

 search of antitumor antibiotics." As many 

 as 2 per cent of all cultures of actinomycetes 

 isolated from soil possess antitumor actiA'ity. 



Considerable information has acciunu- 

 lated concerning the mode of action of some 

 of these antibiotics, especially actinomycin, 

 upon the tumor cells. Robineaux et at. (1958), 

 for example, have shown that in tissue cul- 

 ture, antimitotic activity of actinomycin C 

 is completely repressed by glutathione; cyto- 

 static activity is not affected, however. 

 They suggested that actinomycin possesses 

 at least two mechanisms: antimitotic and 

 cytocidal. 



In speaking of the effect of actinomycin U 

 upon transplantable animal tumors, Sugiura 

 (1960) stated, "The effectiveness, at least 

 temporary, of this antibiotic against human 

 neoplasia (Wilms's tumor, neuroblastoma, 

 rhabdomyosarcoma, lymphosarcoma, Sw- 

 ing's tumor, and melanoma) affords some 

 hope in the attainment of our goal, the cure 

 of cancer in man." 



Various methods for the determination of 

 cytotoxic metabolites formed by microor- 

 ganisms ha\'e been suggested. Perlman el al. 

 (1959) tested a number of antibiotics for 

 inhibition of multiplication of an L cell line 

 of mouse fibroblasts and showed that various 

 actinomycins (Fig. 3) were remarkably ac- 

 tive. 



Antitoxin Activity of Antibiotics 



A'arious antibiotics possess remarkable 

 antitoxin properties. Hinton and Orr (1960), 

 for example, have shown that inhibition of 



