Effects of 5-fluorouracil and a combination of tegafur and uracil (UFT) on nucleotide metabolism in L1210 ascites tumor

Cancer Invest. 1993;11(5):530-3. doi: 10.3109/07357909309011671.

Abstract

Changes in the deoxyribonucleotide pools following a single oral administration of 13 mg/kg of 5-fluorouracil (5-FU) or of 64.8 mg/kg of UFT (a mixed compound of tegafur and uracil) were investigated. We compared their pharmacodynamics and effects on nucleotide metabolism in L1210 ascites tumor on day 3 after intraperitoneal tumor inoculation. The intracellular dTTP pool decreased to half the control level 1-6 hr after the administration of 5-FU. The dTTP pools rapidly recovered after 6 hr. In contrast, UFT kept the intracellular dTTP level to 1/3 to 1/2 of the control level for 24 hr. Either drug elevated the intracellular dATP pools, but decreased dCTP pools. UFT influenced the intracellular dATP and dCTP levels longer than 5-FU. Orally administered UFT seemed to exert a longer and more potent inhibitory effect on thymidylate synthetase than equimolar 5-FU. In view of these results, we suggest that UFT could be a more potent chemotherapeutic drug than 5-FU in oral administration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Deoxyribonucleotides / metabolism*
  • Fluorouracil / pharmacology*
  • Injections, Intraperitoneal
  • Leukemia L1210 / metabolism*
  • Leukemia L1210 / mortality
  • Male
  • Mice
  • Tegafur / pharmacology*
  • Uracil / pharmacology*

Substances

  • Deoxyribonucleotides
  • Tegafur
  • Uracil
  • Fluorouracil