Effects of 5-fluorouracil and a combination of tegafur and uracil (UFT) on nucleotide metabolism in L1210 ascites tumor.
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.
Kakito
H
H
Department of Pharmacy, Mie University School of Medicine, Japan.
Ohkubo
T
T
Kagawa
Y
Y
Inagaki
S
S
Sumida
K
K
Ooi
K
K
Higashigawa
M
M
Sakurai
M
M
D000818:Animals; D003854:Deoxyribonucleotides / Q000378:metabolism*; D005472:Fluorouracil / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000378:metabolism* / Q000401:mortality; D008297:Male; D051379:Mice; D005641:Tegafur / Q000494:pharmacology*; D014498:Uracil / Q000494:pharmacology*
D003854:Deoxyribonucleotides; D005641:Tegafur; D014498:Uracil; D005472:Fluorouracil