Additive formation of antineoplastic 5-fluorouracil nucleosides from 5-fluorouracil by Ehrlich ascites tumor extracts in the presence of ribose 1-phosphate/uridine or deoxyribose 1-phosphate/deoxyuridine.

Abstract

In a study on the enhancement of antitumor effect with 5-fluorouracil or its masked derivatives, the amounts of antineoplastic metabolic precursors, formed from 5-fluorouracil-6-14C in the presence of various substrates by crude enzyme extracts from Ehrlich mouse ascites tumor cells and normal mouse liver were determined. Combinations of uridine plus ribose 1-phosphate and deoxyuridine plus deoxyribose 1-phosphate were effective for the enhancement of 5-fluorouridine and 5-fluorodeoxyuridine formation, respectively. 5-Fluorouridine and 5-fluorodeoxyuridine are, respectively, utilizable for the synthesis of the antineoplastic compounds 5-fluoroUTP and 5-fluoro-2''-deoxyUMP. The coadministration of these substrates with 5-fluorouracil apparently would be advantageous in the enhancement of the antitumor effect of 5-fluorouracil or its masked derivatives.