EFFECTS OF UFT (MIXED COMPOUND OF TEGAFUR AND URACIL) ON CELL-KINETICS AND INHIBITION OF THYMIDYLATE SYNTHASE IN L1210 ASCITES TUMOR

Previous work in our laboratory showed that UFT (mixed compound of teg afur and uracil, molar ratio 1:4, respectively) caused the prolonged r eduction of dTTP in L1210 leukemia cells in comparison with 5-fluorour acil (5-FU). The purpose of this study was to assess the effect of UFT on cell cycle distribution and thymidylate synthase activity of a leu kemia cell line as compared with 5-FU. UFT and 5-FU were orally given to BDF1 mice bearing L1210 ascites tumor on day 3 after the tumor inoc ulation. Cell cycle distribution patterns at 24 hr after the drug admi nistration showed a higher percentage of S phase in tumor cells treate d with UFT than in those treated with 5-FU. Until 6 hr after the oral administration of the drugs, UFT inhibited the incorporation of [H-3]d eoxyuridine into DNA more long than 5-FU did. These results indicated that UFT has longer and stronger inhibitory effects on DNA replication than 5-FU in vivo under the employed experimental conditions (i.e., l ow and single doses of these fluorinated pyrimidines).