100 



NATURE, FORMATION, AND ACTIVITIES 



12 5 



HOURS 



Figure 7. Effect of novol)iocin (1 mg ])er ml) on turbidity and vial)le count of growing cells of E. 



coli; = viable count; = turbidity. (Reproduced from Brock, T. D. and Brock, M. L. Arch. 



Biochem. Biophys. 85: 176-185, 1959.) 



Actinomyciyi 

 Actinomycin is a bacteriostatic agent, 

 active primarily upon gram-positive bac- 

 teria and to a lesser degree upon gram-nega- 

 tive bacteria. It is also active upon certain 

 neoplasms. It is extremely toxic to animals, 

 a factor which limits its utilization in the 

 therapy of infectious diseases and certain 

 forms of cancer. One milligram of actinomy- 

 cin given to mice, rats, or rabl:)its intra- 

 venously, intraperitoneally, subcutaneously, 

 or orally is lethal for 1 kg weight of the 

 animals. Doses as small as 50 /xg per kg 

 injected intraperitoneally daily for 6 days 

 cause death accompanied by severe gross 

 pathological changes, notabl.y a marked 

 shrinkage of the spleen. Actinomycin is 

 rapidly excreted from the body. 



Kawamata and Imanishi (1960) suggested 

 that the carcinogenic effect of actinomycin 

 may be due to its interaction with deoxyri- 

 bonucleic acid. 



Foley (1955) found that the action of ac- 

 tinomycin D upon bacteria consists in inter- 

 ference with pantothenate utilization. This 

 phenomenon could not be confirmed by 

 Slotnick (1957) for B. subtilis. Slotnick 

 (1960) demonstrated that actinomycin D 

 suppresses the assimilation of ammonia by 

 B. suhtilis and inhibits completely the for- 

 mation of certain inducible enzymes. He 

 concluded that this antibiotic interferes in 

 some reactions leading to protein synthesis. 



Kirk (1960) studied the metabolic reac- 

 tion between actinomycin D and DXA and 

 found that the antibiotic has no significant 

 inhibitory effect on the polynucleotide phos- 

 phorylase of Staph, aureus, that it inhibits 

 the incorporation of radioactivity into the 

 HC104-insolul)le fraction when P^-.j^Q^y- 

 adenosine triphosphate is incubated with a 

 crude preparation of the DNA "polymer- 

 ase" enzyme isolated from Escherichia coli, 

 and that it inhibits the transformation of 



