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Studies with Tritiated Mithramycin in C3H Mice¹

Departments of Medicine and Radiology, University of Minnesota Medical Center, Minneapolis, Minnesota 55455

The cytotoxic characteristics of the antibiotic mithramycin were studied by measuring the distribution of tritium-labeled mithramycin in C3H mice. The greatest concentrations of the isotope were in the kidneys and liver. The excretion of mithramycin-³H was rapid, and there was no evidence of metabolism of the carbohydrate moiety to carbon dioxide and water with loss through respiration. Although the concentration in the brain was low, the rate of fall of isotope activity was slower than in the other tissues. Radioautography studies demonstrated concentrations of the isotope in the Kupffer cells of the liver and cells of the renal tubules. The distribution of tritium-labeled mithramycin correlated closely with the known clinical, biochemical, and morphologic effects of administered mithramycin observed during the treatment of neoplasms of the testis, kidney, and brain.

¹ This investigation was supported by Grants CA-3143, CA-05862, CA-08344, CA-08832, and T4 CA-5158 from the National Cancer Institute, USPHS.

Received 11/25/66. Accepted 5/ 2/67.