Abstract
5-Fluorouracil (FUra), a pyrimidine antimetabolite, is
a useful antineoplastic agent. Numerous studies over the
past 30 years have demonstrated that the effects of FUra
are mediated by its anabolism to analogs of pyrimidine
nucleotides (e.g., fluorodeoxyuridine monophosphate)
although the exact cytotoxic mechanism is still unclear
(1). More recently, studies of FUra catabolism have
shown that the degree of catabolism determines the availability of FUra for anabolism and, thereby, may influence
its cytotoxic effects (2). FUra is metabolized by the same
three enzymes that degrade the de novo pyrimidines,
uracil, and thymine (3), with dihydropyrimidine dehydrogenase (DPD) being the initial enzyme in the catabolic
pathway