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Fluoroacetate and Fluorocitrate Antagonism of Tumor Growth Effect of These Compounds on Citrate Metabolism in Normal and Neoplastic Tissue^*

( Departments of Biochemistry and Surgery, College of Physicians and Surgeons, Columbia University, New York, N.Y.)

1. Monofluoroacetate and monofluorocitrate both show carcinostatic activity against the adenocarcinoma 755 grown in C57BL mice.

2. The administration of monofluoroacetate markedly increased the citric acid levels in the 755 tumor and normal brain, heart, and kidney tissue. Monofluorocitrate administration raised the citrate concentration in tumor and kidney tissue but had no effect on the citric acid levels in mouse brain or heart.

3. In vitro studies on seven different experimental mouse neoplasms indirectly indicate that all these tumor tissues possess aconitase activity. However, of all the neoplasms studied, only the adenocarcinoma 755 can efficiently convert fluoroacetate to fluorocitrate as measured by citric acid accumulation in fluoroacetate-poisoned tumor homogenates.

^* This work was supported in part by Grant DRIR 244A(T) from the Damon Runyon Memorial Fund for Cancer Research and, in part, by Grant C-2446 from the National Cancer Institute, of the National Institutes of Health, Public Health Service.

Received 12/19/55.