Ascites tumors provide an almost pure culture of highly malignant cancer cells whose metabolism, unlike that of solid tumors, can be studied in vitro without cell damage. The first measurements of the metabolism of the Ehrlich mouse ascites tumor were carried out in 1950 (131). These cells were found to exhibit, par excellence, the metabolic characteristics that Otto Warburg (The Metabolism of Tumours. London: Constable & Co., 1930) showed to be the property of all malignant tissues, namely, a high anaerobic glycolysis, a large and persistent rate of lactic acid formation in oxygen, and a moderate respiration. The Pasteur effect was quantitatively similar to that of other malignant tumors. The oxygen consumption of ascites cancer cells was considerable in the absence of added substrates, whereas the anaerobic and aerobic glycolysis of washed cells was completely dependent upon the addition of sugars. The rates of anaerobic formation of lactic acid from various hexoses were found to parallel the rates of their phosphorylation by the hexokinase of this tumor. Oxygen consumption was depressed by glycolyzable sugars (Crabtree effect) to a greater extent than was previously observed in experiments with slices of solid tumors. The response of the respiration of ascites cancer cells to auto-oxidizable dyestuffs, and to uncoupling agents such as dinitrophenol, was dependent on the presence of glycolyzable sugars in the suspension medium and the levels of inorganic phosphate therein. These findings have since been confirmed in many laboratories (e.g., Wu, R., and Racker, E. J. Biol. Chem., 234:1036, 1959; Kvamme, E. Acta Physiol. Scandinav. 421204, 1958; Chance, B., and Hess, B. J. Biol. Chem., 23412404, 1959; Slechta, L.; Jakubovic, A.; and Sorm, F. Collection Czechoslov. Chem. Comm., 20:863, 1955). Mitochondria were isolated from the Ehrlich ascites tumor and shown to catalyze the synthesis of ATP coupled to the oxidation of succinate by a dinitrophenol-sensitive mechanism. The rapid breakdown of pyridine nucleotides by these particles was studied. Measurements of various oxidizing and glycolytic enzymes in the ascites tumor cells (131, 190) revealed that the TPN-specific dehydrogenases of the pentose phosphate shunt were as active as in many normal tissues and that this tumor was particularly rich in glutathione reductase.

Other investigations (unpublished) showed that anaerobic and aerobic glycolysis of washed ascites cancer cells, and also the Crabtree effect (but not their endogenous respiration), were unusually dependent upon potassium ions. The stimulatory effect of potassium on the over-all rate of glycolysis could be replaced by ammonium or rubidium, but not by lithium. Evidence was obtained that these actions of potassium resulted from its stimulation of the phosphopyruvate kinase (but not of other glycolytic enzymes) of the Ehrlich ascites tumor.

Studies were also carried out (131) on the bulk proteins and enzymes in the ascitic plasma, the fluid that bathes the ascites cancer cells in the living mouse.