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IDENTIFICATION OF CHANGES IN XENOBIOTIC METABOLISM ENZYME EXPRESSION DURING AGING USING COMPREHENSIVE TRANSCRIPT PROFILING
Citation:
CORTON, C. AND J. S. LEE. IDENTIFICATION OF CHANGES IN XENOBIOTIC METABOLISM ENZYME EXPRESSION DURING AGING USING COMPREHENSIVE TRANSCRIPT PROFILING. Presented at Society of Toxicology Annual Meeting 2007, Charlotte, NC, March 25 - 29, 2007.
Description:
Aging leads to changes in the expression of enzymes and transporters important in the metabolism and fate of xenobiotics in liver, kidney and intestine. Most notable are the changes in a number of CYP and xenobiotic transporter genes regulated by the nuclear receptors PXR, CAR and PPARalpha in the liver. In order to gain a comprehensive understanding of the effects of aging on xenobiotic metabolism, we are using DNA microarray analysis to study the changes that occur in a number of tissues relevant to metabolism of xenobiotic chemicals including the liver at different life stages in mice and rats. We show remarkable changes in phase I, II and III gene expression that are both species-dependent and -independent. We are using this information to create a biologically realistic pharmacokinetic model that predicts altered metabolism of xenobiotics in aged populations.