The Effect of 6-Azauridine Administration on De Novo Pyrimidine Production in Chronic Myelogenous Leukemia*

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Abstract
The rate of de novo pyrimidine production was determined in three patients with chronic myelogenous leukemia before and during therapy with azauridine, an inhibitor of orotidylic acid decarboxylation. A fourth patient was studied only during therapy. The pretreatment rates, estimated by the incorporation of intravenous orotic acid-6-C14 into urinary pseudouri-dine, were 4.2, 10.2, and 15.9 mmoles per day. During therapy the rates, estimated by the incorporation of orotic acid-7-C14 into urinary orotidine, were 25.9, 37.8, 72.0, and 147.6 mmoles per day. In addition the rates of production of uridylic acid during therapy estimated by this method were 11.8, 13.3, 56.0 and 120.2 mmoles per day. These data suggest that during some stages of therapy of chronic myelogenous leukemia with azauridine, there is no evidence for a decrease but instead perhaps evidence for an increase in the whole body rate of uridylic acid production.