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The mechanism of the reversal of 5-fluorouracil cytotoxicity in L5178Y cells by hypoxanthine, adenine and inosine was examined in a cell-free system. A crude extract of the cells possessed high hypoxanthine and adenine phosphoribosyltransferase and purine nucleoside phosphorylase activities. Hypoxanthine (2 mM), adenine (5 mM) and inosine (5 mM) inhibited the nucleotide formation from 5-fluorouracil at 0.2 mM 5-phosphoribosyl 1-pyrophosphate (PRPP). However, at a higher concentration of PRPP (2.5 mM), the inhibition of hypoxanthine was not found. It suggests that the inhibition of 5-fluorouracil metabolism is due to a deficiency of PRPP induced by phosphoribosylation of hypoxanthine and adenine.
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