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Studies on the Biological Action of Malononitriles^*

III. Effect of Malononitrile Administration on Excretion of Thiocyanate in Normal and Walker Carcinoma 256-bearing Rats

( Department of Physiological Chemistry, University of California, School of Medicine, Berkeley, Calif.)

1. No statistically significant difference was noted between the daily excretion of endogenous thiocyanate by normal and by tumor-bearing animals. Neither sex nor the injection of water or propylene glycol (vehicles used for the administration of nitriles) had any influence on this excretion. The statistically established average value for endogenous thiocyanate excretion was 2.3 µM/day for the rat. There is evidence for continuous cyanide formation in the body as a part of the general metabolism.

2. The daily excretion of thiocyanate for 6 days following intraperitoneal administration of single doses of various malononitriles displayed a "trend" toward lower values in the tumor-bearing animals.

3. In confirmation of a previous report (6), the experimental data showed that the activity of malononitriles in retarding tumor growth was not due to release of cyanide, as the percentage conversion of these compounds to cyanide was much smaller than that of the malononitriles without tumor-inhibitory action.

4. The study of the rate of thiocyanate excretion showed that, as compared to malononitrile and benzalmalononitrile, nitro substitution produced a shift in the time of maximum excretion of thiocyanate. The selectivity of the nitro group in causing this shift is presumptive as no other ring substitutions were investigated.

5. No significant changes in the pH of the urine were caused by administration of single doses of nitriles.

^* This work was aided in part by grants from the National Cancer Institute, United States Public Health Service.

Received 10/10/52.