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

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In order to aquire a biochemical fundamental knowledge on the enhancement of antitumor effect with 5-fluorouracil or its masked derivatives, this investigation was undertaken to determine the amounts of antineoplastic metabolic precursors formed from 5-fluorouracil-6-^<14>C in the presence of various substrates by crude enzyme extracts from Ehrlich mouse ascites tumor cells and normal mouse liver. 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 utlizable for the syntheses of the antineoplastic compounds, 5-fluorouridine 5'-triphosphate and 5-fluoro-2'-deoxyuridine 5'-monophosphate. These results suggest that the coadministration of the above substrates together with 5-fluorouracil would be advantageous in the enhancement of the antiumor effect of 5-fluorouracil or its masked derivatives.
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