Molecular Pharmacology, Vol 7, 117-121, Copyright © 1971 by the American Society for Pharmacology and Experimental Therapeutics

Determinants of Responsiveness to 5-Fluorouridine in Transplantable Murine Leukemias

¹ Department of Pharmacology and Division of Oncology, Univeristy of Rochester School of Medicine and Dentistry, Rochester, New York 14620

The antineoplastic agent 5-fluorouridine was therapeutically effective against only the murine leukemias which contained low levels of uridine phosphorylase (EC 2.4.2.3). In such cell lines, degradation of 5-fluorouridine to 5-fluorouracil by uridine phosphorylase was insignificant. The selective toxicity of 5-fluorouridine was enhanced by this enzymatic deletion, since degradation to the less potent 5-fluorouracil is thereby prevented. 5-Fluorouridine, unlike 5-fluorouracil, is highly toxic to the host. Resistance to fluorouridine was characterized by the deletion of uridine kinase (EC 2.7.1.48), not by barriers to transport. On a molar basis, fluorouridine was more than 50 times as effective as fluorouracil in the inhibition of deoxyuridine incorporation into DNA by Leukemia P388 cells.