Regulation of ribosomal RNA synthesis in mammalian cells: effect of toyocamycin.

The present study shows that the antitumor agent toyocamycin (4-amino-5-cyano-7beta-D-ribofuranosylpyrrolo(2-3d)pyrimidine) affects rRNA transcription in Ehrlich ascites cells. This action of the antibiotic is dependent on the amino acid composition of the cell culture medium. In cells incubated in a medium rich in amino acids, the high transcription rate of rRNA is lowered by the addition of 2 X 10(-6) M toyocamycin, while in amino acid starved cells the decreased level of rRNA synthesis remains unaffected. Processing of the 45S rRNA precursor is markedly inhibited by toyocamycin in cells incubated in either medium, indicating that the uptake of the drug is unimpaired by amino acid starvation. Toyocamycin does not affect RNA polymerase I (RNA nucleotidyltransferase EC 2.7.7.6) activity when added to in vitro assay systems derived from cells grown in complete or in amino acid deficient media. The drug prevents the activation of rRNA synthesis following the refeeding of amino acid starved cells without affecting the stimulation of protein synthesis.