抄録
The mechanism of action of phenomycin, an antitumor antibiotic, was studied, using mammalian systems. Phenomycin was observed to inhibit protein synthesis, but not RNA or DNA synthesis in growing HeLa cells. Approximately 50 % inhibition of leucine incorporation into protein was demonstrated at a concentration of 100 mcg/ml of phenomycin when the cells were treated with the antibiotic for 24 hours. Phenomycin significantly inhibited protein synthesis in the lysate of Ehrlich carcinoma cells, although only a slight inhibition was observed with intact cells. Protein synthesis in ribosomal systems of rat liver and rabbit reticulocytes with native mRNA was markedly suppressed by the presence of phenomycin. In reticulocyte ribosomes, polyphenylalanine synthesis with poly U was rather resistant to the action of the antibiotic. The site of action of phenomycin in a proteinsynthesizing system was studied, using rabbit reticulocyte system. It was demonstrated that phenomycin did not affect aminoacyl-SRNA formation but inhibited the amino acid transfer from aminoacyl-SRNA to polypeptide. The non-enzymatic binding of lysyl-SRNA to the ribosomes with poly A or with native mRNA was significantly inhibited by phenomycin. Contrary to the mammalian systems, protein synthesis was not significantly affected by the presence of phenomycin, in an E. coli system. The site of action and selective toxicity of phenomycin are discussed.
