Shoji Inagaki

ENHANCED INCORPORATION OF 1-BETA -D-ARABINOFURANOSYLCYTOSINE BY PRETREATMENT WITH ETOPOSIDE

We examined the effects of timing of administration of etoposide on cytosine arabinoside (ara-C) incorporation into DNA in L1210 ascites tumor. At 1 hr after injection of ara-C, 3-hr and 6-hr pretreatments with 15 mg/kg of etoposide increased ara-C incorporation to more than 200% as compared to that of ara-C given alone. Simultaneous administration of etoposide, however, decreased ara-C incorporation to 33% of that of ara-C alone. These results might explain the previously reported sequence dependency of the antitumor effect of etoposide and ara-C.

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).

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.

Some studies on the determination of indicator transition and its use in the titration of weak basic samples

Abstract In the titration of a weak basic sample, especially in the dilute solution, the transition color of the indicator is not sharp at the equivalence point. In order to avoid the indicator error, the color transition near the equivalence point must be known accurately. The color transition of an acid-base indicator can be calculated from complementary tristimulus data. To ensure accuracy, however, the chemical stoichiometric relationships about the acid-base equilibria are considered. A general expression for determination of the equivalence point is presented and factors influencing the titration are discussed.

Relationship Between the Loss in Weight on Dividing and Humidity, Dustability or Angle of Repose of powders

Humidity, dustability or angle of repose may have relation to the loss in weight on dividingand packaging of powder. The above physical Properties and factors were examined with powders in three forms such as fluffy powder, fine granule and granule. It seems that the loss in weight on dividing of powder changes in proportion to the mixing ratio and the angle of repose, and in inverse proportion to the dispersibility. But the loss of weight may depend more largely on physical factors other than the angle of repose and dispersibility, because the rate of weight loss is different by the form and quality of powder.