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Metabolism of Neoplastic Tissue

XIII. Substrate Competition in Fatty Acid Oxidation in Ascites Tumor Cells^*

( Lankenau Hospital Research Institute and the Institute for Cancer Research, Philadelphia, Pennsylvania)

Ehrlich ascites tumor cells, with their fatty acids labeled by administration of palmitate-1-C¹⁴, were allowed to respire in a phosphate-buffered saline medium in the presence of a range of concentrations of glucose, fructose, lactate, and acetate. All the substrates inhibited the oxidation of endogenous fatty acids, as determined by decreased radioactivity of the respiratory CO₂. In simultaneous experiments with unlabeled cells, but with labeled substrates, it was found that, at low to moderate substrate concentrations, their oxidation roughly corresponded with the suppression of endogenous fatty acid oxidation, indicating a replacement of the latter by the former. At relatively high concentrations of glucose and fructose, however, the inhibition of oxygen uptake (Crabtree Effect) was accompanied by a corresponding decrease in endogenous fatty acid oxidation without concomitant increase in sugar oxidation. The results suggested that fatty acids are physiological substrates for tumor respiration and that their utilization depends partially on the availability of glucose, which is a preferred substrate.

^* This work was supported by grants from the National Institutes of Health, The American Cancer Society, and the United States Atomic Energy Commission.

Received 11/ 5/57.