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A Comparison of the Rate of Recovery from Inhibition of RNA Synthesis in Mouse Liver and Transplantable Glioma¹

Department of Medicine, University of Minnesota Medical Center, Minneapolis, Minnesota 55455

In an attempt to reduce the clinical toxicity of mithramycin by an altered dosage regimen, RNA synthesis was studied in an experimental mouse glioma and in mouse liver at varying times following treatment with mithramycin. There was a marked dissociation between the rate of recovery of these two tissues from the RNA-inhibitory effect produced by mithramycin. Whereas liver rapidly recovered its capacity for RNA synthesis, the recovery of the tumor was delayed. This suggested that an alternate-day dosage regimen might reduce toxicity while maintaining antitumor effect. Extension of such a regimen into clinical studies has given promising results.

¹ This investigation was supported in part by USPHS Research Grants CA-3143, CA-08344, CA-08832, and CA-05862 from the National Cancer Institute.

Received 2/20/67. Accepted 5/23/67.