Date of Award:
Master of Science (MS)
William A. Brindley
William A. Brindley
Steven G. Oberg
William M. Draper
Metabolism of biphenyl by meadow voles (Microtus montanus) liver microsomes was studied by gas liquid chromatography. The microsomal biphenyl hydroxylation of Swiss Webster mice (outbred) was also investigated to provide a species comparison. 4-hydroxybiphenyl (major metabolite), 3-hydroxy biphenyl (minor) and smaller amounts of 2-hydroxybiphenyl were identified as metabolites of biphenyl incubated with vole liver microsomes. Liver microsomes from Swiss mice formed 4-hydroxy biphenyl (major metabolite) and almost equal amounts of 2- and 3-hydroxy biphenyl (minor metabolite). The amount of the hydroxy biphenyls formed by vole liver microsomes was considerably less per milligram of microsomal protein than for mice.
There was NADPH/NADH synergism with the formation of biphenyl hydroxylations in voles. Phenobarbital treatment of voles induced 2-, 3- and 4-hydroxy biphenyl formation, whereas only slight increases were observed after administration of 3-methylcholanthrene or B-naphthoflavone. No changes in the amount of biphenyl 2- hydroxylation of mice followed pretreatment with phenobarbital. However, 3-hydroxylation showed a small increase and 4-hydroxylation was induced. Mice pretreated with 3-methylcholanthrene or B-naphthoflavone were preferentially induced in biphenyl 2-hydroxylation. The reduced hemoprotein difference spectra of microsomal fractions were studied. Only 0.8 nm shift of the Soret peak occurred in liver microsomes from voles pretreated with, 3-methylcholanthrene. The induction and spectral data indicate that 2-, 3- and 4-hydroxylation are associated principally with cytochrome p-450 in voles with little evidence for a substantial role of cytochrome p-448. There is, therefore, a significant species difference between the hepatic microsomal mixed function oxidase system of meadow voles and white mice.
Makary, Moheb H., "Biphenyl Hydroxylation by Vole Hepatic Microsomes" (1981). All Graduate Theses and Dissertations. 8309.
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