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Transcriptional profiling of mouse and human livers at different life stages
Citation:
Lee, J., W. Ward, H. Ren, B. Vallanat, B. D. ABBOTT, AND C. CORTON. Transcriptional profiling of mouse and human livers at different life stages. Presented at Ssociety of Toxicology 49th Annual meeting, Salt Lake City, UT, March 07 - 11, 2010.
Impact/Purpose:
The goal of this study was to identify XMEs that exhibit expression changes at different life stages including fetal, neonatal and the aged. We examined global expression changes using full-genome Affymetrix gene chips and confirmed changes with RT-PCR.
Description:
In the presence offoreign compounds,metabolichomeostasis oftheorganismismaintained by the liver's ability to detoxify and eliminate these xenobiotics. This is accomplished, in part, by the expression ofxenobiotic metabolizing enzymes (XMEs), which metabolize xenobiotics and determine whether exposure will result in toxicity. The goal of this study was to identify XMEs that exhibit expression changes at different life stages including fetal, neonatal and the aged. We examined global expression changes using full-genome Affymetrix gene chips and confirmed changes with RT-PCR. The livers from untreated fetal mice (GDl1.5-GD19) and to a lesser extent neonatal mice (PND 10) exhibited dramatic differences compared to young adult animals including 1)suppression ofphaseIandIIgenes, 2)increasedexpression ofasubset ofphaseIII genes, 3) signatures ofhematopoietic cells, especially nucleated erythrocytes and 4) a pancreaslike signature. A comparison of fetal and adult human livers from archived samples revealed similarities to the mouse results including 1) a general suppression ofXME genes and 2) greater similarityoffetallivertoadultpancreasthanadultliver. Ananalysis oftheliversfromyoung and old mice or humans revealed more subtle changes in gene expression including those in phase III transporters. In addition, we identified gene expression differences between men and women in the young or old groups, respectively, some ofwhich were XMEs. These studies indicate that the livers from fetal or neonatal mice and humans exhibit dramatic changes in XMEs compared to young adults that may lead to differences in the metabolism ofxenobiotics. (This abstract does not necessarily reflect US EPA policy).