RT Journal Article
SR Electronic
T1 Determinants of Responsiveness to 5-Fluorouridine in Transplantable Murine Leukemias
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 117
OP 121
VO 7
IS 2
A1 DAVID KESSEL
A1 REGINA BRUNS
A1 THOMAS C. HALL
YR 1971
UL http://molpharm.aspetjournals.org/content/7/2/117.abstract
AB 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.