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The Effect of 2-Desoxy-D-glucose on Glycolysis and Respiration of Tumor and Normal Tissues

( Biochemical Research Foundation, Newark, Delaware)

The glucose analog, 2-desoxy-D-glucose (2DG), has been shown to inhibit the anaerobic and aerobic glycolysis of glucose (glucolysis) by slices of the rat tumors, Flexner-Jobling carcinoma and Walker 256 carcinoma. The anaerobic glucolysis of slices of rat brain and sections of rat diaphragm was also inhibited by 2DG. Brain was about 7.5 times more sensitive to 2DG than was tumor. Diaphragm was intermediate between brain and tumor in sensitivity toward 2DG.

The type of inhibition appeared to be competitive, since inhibition was reversed by increased glucose in the case of tumor and brain.

2DG also inhibited the anaerobic glycolysis of fructose (fructolysis) by tumor tissue slices. Tumor fructolysis was at least 50 times more sensitive to 2DG than was tumor glucolysis. The anaerobic fructolysis of liver was also inhibited by 2DG, but was about 100 times less sensitive to 2DG than was tumor fructolysis.

2DG did not significantly inhibit the endogenous respiration in any of the tissues studied. Oxidation of glucose by brain tissue slices was inhibited only by a very high proportion of 2DG to glucose, while oxidation of fructose was about 100 times more sensitive to 2DG than was oxidation of glucose.

The possibility is discussed that 2DG in vivo might have a selective inhibitory effect on tumor metabolism.

Received 5/24/54.

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