Substrate Effects on Metabolic Patterns of Pyruvate-2-C" in Tissue Slices* HARRIS BUSCH,~ MORRIS H. GOLDBERG, AND DOLORES

The metabolism of C ~4-1abeled pyruvate in normal and neoplastic tissue has been studied both in vitro (8, 10, 13, 14) and in vivo (3). Although the experiments of the Coris (6) and Warburg (1~) indicated a net production of lactate by tumors in vivo and in vitro, the metabolism of trace quantities of C14-1abeled pyruvate was not found to be significantly different in tumors and other tissues in vitro (10, 13, 14). In contrast, the "metabolic pattern" for pyruvate-2-C 14 differed markedly in tumor and nontumor tissues in vivo (3). Within 3 minutes after injection of the tracer, the nontumor tissues contained 30-80 per cent of the total tissue isotope in the amino acids, glutamic acid, alanine, and aspartic acid (3), while the tumors studied contained less than 5 per cent of the total tissue isotope in these amino acid pools. In the nontumor tissues, the peak for the percentage of total tissue isotope in lactate was uniformly found in the first minute after injection of the pyruvate-2-C 14, and, thereafter, the isotope in lactate dropped rapidly so that at 8 minutes after injection of the tracer, 3-20 per cent of the total tissue isotope remained in lactate. In the 8-minute interval of the study, the isotope in lactate in the tumors always comprised 50-90 per cent of the total in the tissue. The present report indicates the results of an initial at tempt to elucidate the reasons for the differences noted in the metabolism of pyruvate2-C14-in tissues in vivo and in vitro. I t has been found that increasing concentrations of glucose and glutamic acid in the medium surrounding the slice altered the metabolic pattern for pyruvate2-C 14 in the direction of that found in the in vivo experiments.