Citric acid content of normal and tumor tissues in vivo following injection of fluoroacetate.

pyruvate via the Krebs citric acid cycle. Elliot and Grieg (2) concluded that tumor slices converted little or no pyruvate to succinate. They observed the disappearance of keto-acids, but not acid groups, when oxalacetate or pyruvate was added to the media. The observation that little succinate accumulated in the presence of pyruvate and mabonate must be discounted, because at that time the role of oxalacetate was not fully apparent, and none was added to the reaction mixture. Whole homogenate systems were developed in this laboratory (6) for the study of the Krebs oxidation cycle, and, when whole tumor homogenates were studied with oxalacetate added to the medium (8), oxygen uptake was almost completely lacking in comparison with several normal tissues. Potter, Pardee, and Lyle (9) found that citrate formation in homogenates of tumor was very low compared to that in normal tissues, and utilization of oxal acetate was equally small. In experiments with glycolyzing tumor homogenates, Potter and LePage (7) observed that tumor homogenates, even while maintaining their ATP through gly colysis, could not oxidize oxalacetic acid via the Krebs cycle, since essentially no citric acid was ac cumulated under anaerobic conditions. The work of Buffa and Peters (1 ) offered a means for testing the ability of tumor to produce citrate in vivo, since oxidation of citric acid is prevented and the compound accumulates following injections of sodium fluoroacetate.