Influence of glucose antimetabolites on the Walker tumor.

A large number of antimetabolites of nucleic acid components have been tried as antitumor agents (11). While some have retarded tumor growth, they are in general toxic to the host ani mal. This is perhaps to be expected, since protein synthesis is an essential phenomenon in all tissues. In the studies to be described, we have at tempted to interfere with the energy sources of the cell. Since the utilization of glucose by the glycolytic pathway appears to be more important for the malignant than the normal cell, the effects of glucose antimetabolites on tumor growth were studied at dosage levels which were not obviously toxic to the animal. Glucosamine has been tried as an antitumor agent by a number of workers, with inconclusive or negative results (2, 4, 6-8, 12, 13, 15-17) after the original promising observations of Quastel and Cantero (10). In most cases, however, a single daily dose of the test material was used. 2-DeoxyD-glucose (2DG) appears to have produced some suppression of tumor growth or glycolysis (5, 14, 20, 21). Since compounds of this type are readily excreted by the kidney, effective levels of the antimetabolite were probably present for only a very short time. In the present studies, we have used multiple daily doses of glucosamine and 2-deoxyD-glucose to achieve a more constant exposure to the compounds. The amount of glucosamine em ployed was generally at least double that reported by other observers. Both compounds produced sig nificant reductions in tumor growth at levels which did not seriously affect the health of the host.