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 admin istration of 13 mg/kg of 5-fluorouracil (5-FU) or of 64.8 mglkg of UFT (a mixed compound of tegafur and uracil) were investigated. We compar ed their pharmacodynamics and effects on nucleotide metabolism in L121 0 ascites tumor on day 3 after intraperitoneal tumor inoculation. The intracellular dTTP pool decreased to half the control level 1-6 hr aft er 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 intracellula r dATP and dCTP levels longer than 5-FU. Orally administered UFT seeme d to exert a longer and more potent inhibitory effect on thymidylate s ynthetase than equimolar 5-FU. In view of these results, we suggest th at UFT could be a more potent chemotherapeutic drug than 5-FU in oral administration.