Alterations in human pyrimidine metabolism as a result of therapy with 6-azauridine.

Biochemical proccr are described which have been found useful in the s tudy of normal pyrimidine Inctabolism as influenced by 6-azm~ridine. One technic involves the t rapping of radioactive carbon dioxide liberated from erotic acid-7-C ~4 during the conversion of this compound to uridine nucleotides by isolated leukocytes in vitro. The susceptibility of this conversion to inhibition by azauridine 5 ' -phosphate derived metabolically from azauridine in rive or in vitro has been measured. The accumulation of erotic acid and orotidine by patients with leukemia t reated with azauridine has been quant i ta ted by ion-exchange analysis of the urine from these patients. Another indication of the effect of azauridine on the metabolism of erotic acid has been obtained by intravenous injection of a tracer dose of erotic acid-7-C 14. Pret rea tment with azauridine of pat ients with neoplastic disease decreased the conversion of this pyrimidine to respiratory C:402 and uridine nucleotides and increased the ur inary excretion of unchanged erotic acid.