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.
In order to acquire 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-6-14C 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 utilizable 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 antitumor effect of 5-fluorouracil or its masked derivatives.
D000818:Animals; D001201:Ascites / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology / Q000378:metabolism*; D003857:Deoxyuridine / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology; D008297:Male; D051379:Mice; D012267:Ribosemonophosphates / Q000378:metabolism; D014529:Uridine / Q000031:analogs & derivatives* / Q000378:metabolism
D012267:Ribosemonophosphates; C031154:ribose 1-phosphate; C031302:2-deoxyribose 1-phosphate; D005472:Fluorouracil; D003857:Deoxyuridine; D014529:Uridine