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

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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.<BR>These observations indicate that these anticancer drugs may alter the biological activity of many other drugs which will be administered simultaneously.
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