David Kessel, Regina Bruns, Thomas C. Hall
Mar 1, 1971
Citations
0
Influential Citations
20
Citations
Quality indicators
Journal
Molecular pharmacology
Abstract
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.