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dc.contributor.advisorHalpert, James R.en_US
dc.contributor.authorStevens, Jeffrey Charles, 1963-
dc.creatorStevens, Jeffrey Charles, 1963-en_US
dc.date.accessioned2013-03-28T10:14:07Z
dc.date.available2013-03-28T10:14:07Z
dc.date.issued1988en_US
dc.identifier.urihttp://hdl.handle.net/10150/276700
dc.description.abstractThe steroid androstenedione has been shown to be a valuable tool for the study of selective inactivation of rat liver cytochrome P-450 isozymes. The validity of this method was investigated using microsomes, purified cytochromes P-450, cytochrome P-450 antibodies, and the mechanism-based inactivator chloramphenicol. Enzyme inactivation and antibody inhibition studies show that microsomes from phenobarbital- and non-phenobarbital-treated rats are needed to accurately monitor the inactivation of the major phenobarbital-inducible P-450 isozyme (PB-B) and of the major constitutive androstenedione 16-alpha hydroxylase (UT-A). Enzyme inactivation studies showed that the antibiotic chloramphenicol caused different rates of NADPH-dependent enzyme inactivation among four androstenedione hydroxylases (16-beta > 6-beta > 16-alpha > 7-alpha). The results with twelve chloramphenicol analogs show that their selectivity as cytochrome P-450 inactivators is dependent upon at least three structural features: (1) the number of halogen atoms, (2) the presence of a para-nitro group on the phenyl ring, and (3) substitutions on the ethyl side chain.
dc.language.isoen_USen_US
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subjectChloramphenicol -- Toxicology.en_US
dc.subjectIsoenzymes -- Effect of drugs on.en_US
dc.subjectAntibiotics -- Toxicology.en_US
dc.subjectCytochrome P-450.en_US
dc.titleSelective inactivation of four rat liver microsomal androstenedione hydroxylases by chloramphenicol analogsen_US
dc.typetexten_US
dc.typeThesis-Reproduction (electronic)en_US
dc.identifier.oclc20765782en_US
thesis.degree.grantorUniversity of Arizonaen_US
thesis.degree.levelmastersen_US
dc.identifier.proquest1333427en_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplinePharmacology and Toxicologyen_US
thesis.degree.nameM.S.en_US
dc.identifier.bibrecord.b2330389xen_US
refterms.dateFOA2018-06-23T00:42:16Z
html.description.abstractThe steroid androstenedione has been shown to be a valuable tool for the study of selective inactivation of rat liver cytochrome P-450 isozymes. The validity of this method was investigated using microsomes, purified cytochromes P-450, cytochrome P-450 antibodies, and the mechanism-based inactivator chloramphenicol. Enzyme inactivation and antibody inhibition studies show that microsomes from phenobarbital- and non-phenobarbital-treated rats are needed to accurately monitor the inactivation of the major phenobarbital-inducible P-450 isozyme (PB-B) and of the major constitutive androstenedione 16-alpha hydroxylase (UT-A). Enzyme inactivation studies showed that the antibiotic chloramphenicol caused different rates of NADPH-dependent enzyme inactivation among four androstenedione hydroxylases (16-beta > 6-beta > 16-alpha > 7-alpha). The results with twelve chloramphenicol analogs show that their selectivity as cytochrome P-450 inactivators is dependent upon at least three structural features: (1) the number of halogen atoms, (2) the presence of a para-nitro group on the phenyl ring, and (3) substitutions on the ethyl side chain.


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