Assessing Hepatic Gene Expression in Response to Xenobiotic Exposure in Mice

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 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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Animal and Poultry Sciences

Department dc:contributor.department

Animal and Poultry Sciences

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2007

Author dc:creator

• Boorgula, Smitha

Chair dc:contributor.committeechair

• Lewis, Ronald M.

Committee members dc:contributor.committeemember

• Wong, Eric A.
• Blodgett, Dennis J.
• Jiang, Honglin

• Ergotamine
• Gene expression
• Hepatic phase I and II enzymes
• Sulforaphane

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

etd-05042007-222410

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/32186