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Journal of Pharmacology And Experimental Therapeutics, Vol. 133, Issue 3, 335-342, 1961
Copyright © 1961 by American Society for Pharmacology and Experimental Therapeutics

PHARMACOLOGY OF MITOMYCIN C II. RENAL EXCRETION AND METABOLISM BY TISSUE HOMOGENATES

Herbert S. Schwartz 1 and Frederick S. Philips 1

1 Sloan-Kettering Division, Graduate School of Medical Sciences, Cornell University, New York, N. Y.

Mitomycin C disappears rapidly from the plasma of dogs and rats. One-third or less can be recovered unchanged in the urine. In the dog renal excretion appears to occur by glomerular filtration. The agent is freely diffusible from dog plasma.

In vitro mitomycin C is metabolized by rat tissue homogenates of which liver is the most active. The metabolism is characterized by loss of antibiotic potency and by changes in ultraviolet absorption spectrum. In liver homogenates oxygen inhibits the metabolizing system whereas nicotinamide stimulates and partially protects from spontaneous loss of activity. It is suggested that the inactivation is due to reductive transformation.

The mode of action of mitomycin has been discussed in the light of its rapid inactivation in vivo.

Submitted on February 27, 1961




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V. N. Iyer and W. Szybalski
Mitomycins and Porfiromycin: Chemical Mechanism of Activation and Cross-linking of DNA
Science, July 3, 1964; 145(3627): 55 - 58.
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H. S. Schwartz, J. E. Sodergren, and F. S. Philips
Mitomycin C: Chemical and Biological Studies on Alkylation
Science, November 29, 1963; 142(3596): 1181 - 1183.
[Abstract] [PDF]


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Copyright © 1961 by the American Society for Pharmacology and Experimental Therapeutics.