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 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).
Kagawa
Y
Y
Department of Hospital Pharmacy, Mie University School of Medicine, Japan.
Ohkubo
T
T
Higashigawa
M
M
Ido
M
M
Kakito
H
H
Inagaki
S
S
Kojima
M
M
Ooi
K
K
Sakurai
M
M
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*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D005641:Tegafur; D014498:Uracil; D013940:Thymidylate Synthase; D003857:Deoxyuridine