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5'-Deoxy-5-fluorouridine (5'-DFUR) was parenterally and orally effective on various transplantable tumors and its activity was better than that of other fluorinated pyrimidines. However, like 5-fluorouracil and 2'-deoxy-5-fluorouridine (FUdR), 5'-DFUR was ineffective on L1210 leukemia resistant to 5-fluorouracil, suggesting that it would exert its antitumor activity through converted 5-fluorouracil. In tissue culture, 5'-DFUR inhibited the growth of various tumor cells similarly to ther fluorinated pyrimidines. However, 5'-DFUR was unique in that uridine completely reversed its inhibitory effect. Enzymological study clarified that uridine inhibited the conversion of 5'-DFUR to 5-fluorouracil by a uridine phosphorylase, in parallel to its reverse effect on cell growth inhibition by 5'-DFUR. Furthermore, a subline of L1210 leukemia resistant to 5'-DFUR but not to 5-fluorouracil was found to lack the uridine phosphorylase. These results indicate that 5'-DFUR is a depot form of 5-fluorouracil which can be promptly activated by uridine phosphorylase. In addition, the uridine phosphorylase was found to be abundant in sarcoma-180 solid tumor, leading to a significantly higher concentration of converted 5-fluorouracil in this tumor than in other normal tissues. This provides a good explanation for the high chemotherapeutic index of 5'-DFUR against this tumor, which may be applicable also for other tumors.

The immunosuppressive effect of 5'-deoxy-5-fluorouridine (5'-DFUR, Ro 21-9738) was examined for both humoral and cell-mediated immunity in mice in comparison with that of 5-fluorouracil and Ftorafur (FT-207). By both oral and intraperitoneal administration, 5'-DFUR was found to be much less suppressive than 5-fluorouracil and FT-207 in all immune responses tested; hemolysin plaque-forming cells, serum hemolysin titer, delayed-type hypersensitivity and allogeneic tumor rejection. Furthermore, 5'-DFUR did not induce any reduction in either the spleen weight, thymus weight, total spleen cell number, or peripheral leucocyte number.

5'-Deoxy-5-fluorouridine (5'-DFUR) exhibits antitumor activity through its conversion to 5-fluorouracil by uridine phosphorylase (UPase) in mice. This mode of activation was confirmed by the fact that a mutant strain of Micrococcus flavus resistant to 5'-DFUR but sensitive to 5-fluorouracil was isolated and found to be deficient in UPase activity. Furthermore, since the enzyme level in tumor tissue should be useful as an indicator for therapy with 5'-DFUR, a simple assay method for the enzyme activity with use of the above bacterium was developed, in which the amount of 5-fluorouracil cleaved from 5'-DFUR by the enzyme was estimated through its antibacterial activity without separation from 5'-DFUR. This method is simple and efficient for handling a large number of samples.