Species differences in the metabolism and macromolecular binding of methapyrilene: a comparison of rat, mouse and hamster
Autor: | R. C. Kammerer, Lampe Ma |
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Rok vydání: | 1990 |
Předmět: |
Male
Cytochrome Macromolecular Substances Health Toxicology and Mutagenesis Methapyrilene Hamster Thymus Gland Toxicology Biochemistry Mice Species Specificity Cricetinae mental disorders medicine Animals Carbon Radioisotopes Carcinogen Pharmacology Mice Inbred ICR biology Rats Inbred Strains DNA General Medicine Metabolism Monooxygenase biology.organism_classification Rats Liver Microsoma Microsomes Liver biology.protein Microsome Cattle human activities medicine.drug |
Zdroj: | Xenobiotica. 20:1269-1280 |
ISSN: | 1366-5928 0049-8254 |
DOI: | 10.3109/00498259009046626 |
Popis: | 1. The metabolism of methapyrilene (MPH) by rat, hamster and mouse liver microsomes in vitro was investigated together with the binding of 14C-MPH to calf thymus DNA after metabolic activation. 2. Both quantitative and qualitative differences in MPH metabolism were observed in these three species. Mouse liver microsomes catalyse the formation of two novel isomers of hydroxypyrdylmethapyrilene (hydroxypyridyl-MPH) as determined by mass spectral analysis. N,N'-Didesmethylmethapyrilene (didesmethyl-MPH) was formed in detectable quantities only when hamster liver microsomes were used. 3. Incubation of liver microsomes from all three species catalysed the binding of 14C-MPH to exogenous DNA, which was quantitatively similar for all three species. The effect of the cytochrome P-450 inhibitor, 2,4-dichloro-6-phenylphenoxyethylamine (DPEA), and methimazole, a flavin-dependent monooxygenase inhibitor, on binding differed significantly for the three species studied. |
Databáze: | OpenAIRE |
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