Fluoroacetate and fluorocitrate antagonism of tumor growth; effect of these compounds on citrate metabolism in normal and neoplastic tissue.

Sodium monofluoroacetate has been shown by Buffa and Peters (1) and Potter and Busch (9) to produce a marked increase in the citric acid con tent of various tissues of animals following injec tions of lethal doses of this compound. Subsequent ly, Buffa et al. showed that the administered fluoroacetate was converted to a fluorinated tn carboxylic acid (s). This compound, a potent corn petitive inhibitor of the enzyme aconitase, proved to be monofluorocitrate (6, 7). The reported low aconitase activity observed in most neoplasms (13) prompted us to compare the carcinostatic activities of monofluoroacetate and monofluorocitrate in the hope that these corn pounds could profitably be employed in some studies of combination cancer chemotherapy (11, 1@)being conducted in our laboratories.