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- W2415436172 abstract "The metabolic reactions leading to cytotoxicity of 5-fluorouracil (FUra) were examined in cultured mouse T-cell lymphoma cells. FUra is phosphoribosylated by orotic acid phosphoribosyl transferase, the second to last enzyme in de novo pyrimidine biosynthesis. Mutants with altered capacities to phosphoribosylate orotic acid in vitro have similarly altered capacities to phosphoribosylate FUra in vivo and in vitro. The sensitivity of these mutant lymphoma cell lines to FUra is momotonically related to their capacity to phosphoribosylate FUra. This phosphoribosylation requires pyrophosphoribosyl phosphate, an intracellular metabolite whose concentration can be regulated in vivo. Purines, which lower the concentration of pyrophosphoribosyl phosphate in cultures of wild type cells, can protect these cells from FUra toxicity. Conversely, purines that do not affect intracellular pyrophosphoribosyl phosphate content do not affect FUra mediated growth inhibition and cytotoxicity. This protection from FUra toxicity by purines requires the presence of the appropriate purine salvage enzymes. Analogous observations with purines on FUra cytotoxicity were made in other cell lines from rat, mouse, and marmoset, indicating that the metabolic activation of FUra by phosphoribosylation may be prevalent." @default.
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- W2415436172 date "1979-03-01" @default.
- W2415436172 modified "2023-09-23" @default.
- W2415436172 title "Metabolism of 5-fluorouracil in cultured cells. Protection from 5-fluorouracil cytotoxicity by purines." @default.
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