The Effect of Chemotherapeutic Agents upon the Metabolism of Intact Human Cancer Cells: an in Vitro Technic for Cell Sensitivity.

The effect of certain chemotherapeutic agents upon the metabolism of human ascites and leukemic leukocytes was investigated. Human leukemic blast cells show 2-3 times the respiratory activity of “chronic” cells. From a study of the effects of eight chemotherapeutic drugs upon the respiration of human leukemic leukocytes and human ascites cells, relative index of cell sensitivity was obtained. The alkaloid, vinbiastine sulfate, and the alkylating agents, triethylenethiophosphoramide and nitrogen mustard, were found to be more toxic to human cancer cells than the antimetabolites, 6-mercaptopurine, 8-azaguanine, aminopterin, diazouracil, or prednisone. Stimulation of aerobic glycolysis was found for all chemicals except aminopterin (no effect) and nitrogen mustard (inhibition). No correlation between stimulation of lactic acid production and inhibition of respiration was found. Stimulation of lactic acid production could be produced under conditions where respiration was unchanged. Only nitrogen mustard differed in that inhibition of respiration always accompanied inhibition of lactic acid production. Most chemotherapeutic agents tested are Pasteur effect inhibitors. An unusual stimulation of glucose disappearance to products unknown as yet was caused by 6-mercaptopurine in all cells tested. The potential usefulness of a cell sensitivity test in clinical chemotherapy is discussed.