Assessing Hepatic Gene Expression in Response to Xenobiotic Exposure in Mice

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dc.contributor.authorBoorgula, Smithaen
dc.contributor.committeechairLewis, Ronald M.en
dc.contributor.committeememberWong, Eric A.en
dc.contributor.committeememberBlodgett, Dennis J.en
dc.contributor.committeememberJiang, Honglinen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2014-03-14T20:35:00Zen
dc.date.adate2007-05-23en
dc.date.available2014-03-14T20:35:00Zen
dc.date.issued2007-04-12en
dc.date.rdate2012-04-27en
dc.date.sdate2007-05-04en
dc.description.abstractXenobiotics are plant derived compounds metabolized by phase I and II liver enzymes. Phase I enzymes increase, and phase II enzymes decrease, xenobiotic toxicity. Xenobiotics considered were ergotamine, associated with fescue toxicosis, and sulforaphane, a phase II inducer. Hypothesized responses in liver gene expression and enzyme activity due to exposure to these xenobiotics were tested. Polymorphic mice were gavaged with sulforaphane, ergotamine or control over four daily dosing periods (2, 5, 8 and 11 d), with at least 5 mice per treatment. Mice were killed and livers collected 24 h after last dosing. With ergotamine, expression of phase II genes catecholâ Oâ amine methyltransferase 1 (P = 0.009) on d 8, and glutathioneâ Sâ transferase (Gst) mu1 (Gstm1; P = 0.049) on d 11 was increased, and sulfotransferase 5a1 on d 11 decreased (P = 0.02). Sulforaphane increased expression of cytochrome P450 1a2 on d 5 (P = 0.02) and flavin containing monooxygenases 1 on d 11 (P = 0.002), both phase I genes. It also increased expression of a phase II gene transcription factor (P = 0.03) and quinone reductase 02 (P = 0.007) on d 5, and Gstm1 on d 8 (P = 0.04) and d 11 (P = 0.01). Moreover, sulforaphane treated mice had higher (P < 0.05) Gstm1 expression across days. Among enzymes, only sufloraphane treated mice had higher (P < 0.05) Gst activity. The increase in both Gstm1 expression and Gst activity indicate a consistent benefit of sufloraphane on phase II enzyme activity.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-05042007-222410en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-05042007-222410/en
dc.identifier.urihttp://hdl.handle.net/10919/32186en
dc.publisherVirginia Techen
dc.relation.haspartSBoorgula_ETD.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectErgotamineen
dc.subjectGene expressionen
dc.subjectHepatic phase I and II enzymesen
dc.subjectSulforaphaneen
dc.titleAssessing Hepatic Gene Expression in Response to Xenobiotic Exposure in Miceen
dc.typeThesisen
thesis.degree.disciplineAnimal and Poultry Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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