In an attempt to establish a better cancer chemotherapy, the metabolism of fluoropyrimidines was investigated in cancer patients.
Both uridine phosphorylase (UrdPase) and thymidine phosphorylase (dThdPase) activity were estimated, using resected stomach or breast cancer specimens as mate rial. Autopsy specimens were also used to determine the whole body distribution of the enzymes in patients with gastric cancer.
As a result, it was demonstrated that dThdPase activity was dominant compared to that of UrdPase. Accordingly, it was considered that 5-fluorouracil (FUra) wasmainly activated, via 5-fluoro-2-deoxyuridine (FdUrd), to produce 5-fluoro-2-deoxy - uridine 5-monophosphate (FdUMP), an active form of FUra. Further, it was also observed that both 1-(2-tetrahydrofurany1)-5-fluorouracil (FT) and 5'-deoxy-5-fluorouridine (5'-DFUR) were activated by dThdPase to form FUra. It was empha sized that this dThdPase activity was over 5-fold higher in tumor tissues than in nor-mal tissues. This observation would indicate that the compounds would exert a tumor-selective toxicity in cancer patients.
