Drug effects on a target metabolic pathway and on mouse tumor growth: azauridine and decarboxylation of orotic acid-7-C-14.

An attempt has been made to relate the effect of a drug on a metabolic pathway, pre sumed to be its locus of action, to the tumor-inhibitory activity of the drug. Azauridine was administered subcutaneously to mice with five different ascites tumors, and growth was measured by total ascites cell counts. Aliquots of ascites tumor cells were incubated with orotic acid-7-C14, and the C14O2evolved was taken as a measure of orotidylic decarboxylase activity. Whereas graded dose-related tumor suppression was generally seen, inhibition of decarboxylation of orotic acid ordinarily did not parallel the effect on tumor growth. The basis for discrepancy is discussed. Attempts to predict relative in vivo sensitivity of the five tumors by azauridine effects on decarboxylation of orotic acid in vitro were unsuccessful.