Title page for ETD etd-05042007-222410


Type of Document Master's Thesis
Author Boorgula, Smitha
Author's Email Address smithab@vt.edu
URN etd-05042007-222410
Title Assessing Hepatic Gene Expression in Response to Xenobiotic Exposure in Mice
Degree Master of Science
Department Animal and Poultry Sciences
Advisory Committee
Advisor Name Title
Lewis, Ronald M. Committee Chair
Blodgett, Dennis J. Committee Member
Jiang, Honglin Committee Member
Wong, Eric A. Committee Member
Keywords
  • Ergotamine
  • Gene expression
  • Hepatic phase I and II enzymes
  • Sulforaphane
Date of Defense 2007-04-12
Availability unrestricted
Abstract
Xenobiotics 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 catechol–O–amine methyltransferase 1 (P = 0.009) on d 8, and glutathione–S–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.
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