Studies of the effects of treatment with 5-flourouracil alone and in combination with either cyclophosphamide, methotrexate, or methyl-CCNU on hepatic drug-metabolizing enzymes in murine L1210 leukemia.
Studies have been conducted on liver microsomal enzymes of B6D2F(1) mice bearing a Day 4 L1210 ascites tumor after treatment with a single intraperitoneal injection of 5-fluorouracil (FUra) alone, and in combination with either cyclophosphamide (CP), methotrexate (MTX), or methyl-CCNU (MeCCNU). FUra (200 mg/kg) alone did not alter either ethylomorphine N-demethylase, aniline hydroxylase, or neotetrazolium reductase activities as compared to untreated nontumor-bearing mice on Days 2, 4 and 6 after treatment. FUra (50 mg/kg)d plus CP (200 mg/kg) decreased neotetrazolium reductase activity 17% on Days 4 and 6 after treatment and the enzyme activity then returned to control levels on Day 8. Ethyl morphine N-demethylase and aniline hydroxylase, or neotetrazolium reductase activities on Days 1, 2, 4 and 6 after treatment. FUra (50 mg/kg) plus MeCCNU (21 mg/kg) did not affect either ethylmorphine N-demethylase or aniline hydroxylase activities on Days 1, 2, 4, 6 and 8 after treatment. However, neotetrazolium reductase activity was decreased 15% on Day 2 and then returned to control levels on Day 4. These results indicate that treatment of mice bearing the L1210 ascites tumor with an optimal single does of FUdra alone and in combination with either CP, MTX or MeCCNU does not have marked or prolonged effects on liver microsomal drug-metabolizing enzyme activities.
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology; D004347:Drug Interactions; D005472:Fluorouracil / Q000494:pharmacology*; D007939:Leukemia L1210 / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology; D051379:Mice; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism*; D012673:Semustine / Q000494:pharmacology
D012673:Semustine; D003520:Cyclophosphamide; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D005472:Fluorouracil; D008727:Methotrexate