Species differences in the metabolism and macromolecular binding of methapyrilene: a comparison of rat, mouse and hamster

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. M...

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Bibliographic Details
Published inXenobiotica Vol. 20; no. 12; p. 1269
Main Authors Lampe, M A, Kammerer, R C
Format Journal Article
LanguageEnglish
Published England 1990
Subjects
Animals
Carbon Radioisotopes
Cattle
Cricetinae
DNA - metabolism
Liver - metabolism
Macromolecular Substances
Male
Methapyrilene - metabolism
Mice
Mice, Inbred ICR
Microsomes, Liver - metabolism
Rats
Rats, Inbred Strains
Species Specificity
Thymus Gland - metabolism
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Summary: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.
ISSN:0049-8254
DOI:10.3109/00498259009046626