Effects of 5-Fluorouracil, 1-(2-Tetrahydrofuryl)-5-fluorouracil and 1-(n-Hexylcarbamoy1)-5-fluorouracil on Drug-metabolizing Enzyme Activities in Mouse Liver

Abstract

Effects of 5-fluorouracil (5-FU), 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) and 1-(n-hexylcarbamoyl)-5-fluorouracil (HCFU) on drug-metabolizing enzyme activities were studied with liver microsomes from male and female mice. Body and liver weights decreased significantly in male mice treated with 5-FU but not in FT-207-and HCFU-administered male mice. Contents of liver microsomal protein increased slightly in 5-FU-, HCFU-and FT-207-treated female mice and significantly diminished in HCFU-treated male mice. Serum GPT activities in these treated male mice remained unchanged. Cytochrome P-450 contents in 5-FU-and FT-207-treated mice of both sexes significantly increased, and aniline hydroxylase activities were slightly elevated in 5-FU-treated male mice, while they were significantly elevated in FT-207-treated female mice. A rise of aminopyrine Ndemethylase activities were found significantly in FT-207-treated female mice and slightly in 5-FU-and HCFU-treated female mice. The effect of FT-207 treatment on drug-metabolizing enzyme activities were generally greater in females than in males.These observations indicate that these anticancer drugs may alter the biological activity of many other drugs which will be administered simultaneously.