title: Effects of UFT (mixed compound of tegafur and uracil) on cell kinetics and inhibition of thymidylate synthase in L1210 ascites tumor.
abstract: Previous work in our laboratory showed that UFT (mixed compound of tegafur and uracil, molar ratio 1:4, respectively) caused the prolonged reduction of dTTP in L1210 leukemia cells in comparison with 5-fluorouracil (5-FU). The purpose of this study was to assess the effect of UFT on cell cycle distribution and thymidylate synthase activity of a leukemia 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 inoculation. Cell cycle distribution patterns at 24 hr after the drug administration showed a higher percentage of S phase in tumor cells treated with UFT than in those treated with 5-FU. Until 6 hr after the oral administration of the drugs, UFT inhibited the incorporation of [3H] deoxyuridine 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., low and single doses of these fluorinated pyrimidines).
authors.affiliation: Department of Hospital Pharmacy, Mie University School of Medicine, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kagawa
authors.forename: T
authors.initials: T
authors.lastname: Ohkubo
authors.forename: M
authors.initials: M
authors.lastname: Higashigawa
authors.forename: M
authors.initials: M
authors.lastname: Ido
authors.forename: H
authors.initials: H
authors.lastname: Kakito
authors.forename: S
authors.initials: S
authors.lastname: Inagaki
authors.forename: M
authors.initials: M
authors.lastname: Kojima
authors.forename: K
authors.initials: K
authors.lastname: Ooi
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D003857:Deoxyuridine / Q000378:metabolism; D004338:Drug Combinations; D007939:Leukemia L1210 / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D005641:Tegafur / Q000494:pharmacology*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors*; D014498:Uracil / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004338:Drug Combinations; D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D003857:Deoxyuridine