In vivo effect of hydroxyurea on orotic acid synthesis.

Hydroxyurea is thought to inhibit DNA synthesis but the site of inhibition has not been established. The urinary excretion of orotic acid was measured in 6 patients, 5 with acute leukemia and 1 with metastatic melanoma, receiving 6-azauridine which is known to inhibit orotidylic decarboxylase. The orotic aciduria observed in these patients was reversed by the addition of hydroxyurea, suggesting inhibition of de novo pyrimidine biosyn thesis at a step prior to the formation of orotic acid. No clear-cut potentiation of a chemotherapeutic effect of this combination of drugs was observed.