Studies on the Mechanism of Inhibition of Tumor Growth by the Enzyme Glutaminase1

The Gardner 6C3HED lymphosarcoma, Leukemia L-1210, and Leukemia L-1210/aza in ascites form were inhibited in in vivo experiments by a highly purified preparation of glutaminase-asparaginase from a pseudomonad. The glutamine con tent of tumors was measured by an enzymatic micromethod. The results showed that glutaminase-treated tumors were depleted of free glutamine. The glutamine-synthetase activity in tissues of normal mice has been compared with that of tumor cells. Tumor tissues showed lower activity of this enzyme than did normal tissues. Glycine-'4C and adenine-14C incorporation studies in vivo indicated the impairment of both the de novo and the reutilization pathways of purine synthesis. Combination therapy with azaserine-enzyme and 8-azaguanine-enzyme produced an augmentation of tumor inhibition.