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( McGill-Montreal General Hospital Research Institute, 3619 University Street, Montreal, P.Q., Canada, and Institute for Cancer Research, Philadelphia, Pennsylvania)
Interrelationships in the oxidation of glucose and fatty acids by cells of the ascites hepatoma 98/15 were studied with the aid of C14-labeled acids. Butyrate-1-C14, decanoate-1-C14, laurate-1-C14, and palmitate-1-C14 were readily oxidized to CO2 when incubated at 37° C. The rate, which was approximately the same for all four acids on a molar basis, accounted for from 4 to about 17 per cent of the total respiration. The two shorter-chain acids had little or no effect on respiration, but the two higher-chain acids at their optimal concentrations markedly stimulated respiration. This respiratory enhancement was only partially accounted for by oxidation of the added fatty acid. Added glucose had little effect on butyrate oxidation but markedly depressed that of the other acids.
Decanoate and the higher fatty acids overcame the approximately 40 per cent inhibition of respiration caused by glucose addition, their effects resembling those of dinitrophenol. At the same time, glucose initially prevented the otherwise inhibitory effects on respiration of fatty acids present in higher concentration. The data are interpreted as confirming previous suggestions that fatty acids uncouple phosphorylation from oxidation in tumor cells and further indicate that glucose alleviates the resultant adenosine triphosphate (ATP) depletion by providing "glycolytic" ATP.
* Aided by grants from the National Cancer Institute, of the National Institutes of Health, and the American Cancer Society, Inc.
Research Associate of the National Cancer Institute of Canada. Much of this work was performed while this author was a summer visitor at the Institute for Cancer Research.
Research Fellow of the Japanese Government on leave from the Institute for Tuberculosis and Leprosy, Tohoku University, Sendai, Japan.
Received 1/27/60.
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