Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9017736 | Toxicology and Applied Pharmacology | 2005 | 8 Pages |
Abstract
Macrophage activators (MA), peroxisome proliferators (PP), and oxidative stressors/reactive metabolites (OS/RM) all produce oxidative stress and hepatotoxicity in rats. However, these three classes of hepatotoxicants give three distinct gene transcriptional profiles on cDNA microarrays, an indication that rat hepatocytes respond/adapt quite differently to these three classes of oxidative stressors. The differential gene responses largely reflect differential activation of transcription factors: MA activate Stat-3 and NFkB, PP activate PPARa, and OS/RM activate Nrf2. We have used gene signature profiles for each of these three classes of hepatotoxicants to categorize over 100 paradigm (and 50+ in-house proprietary) compounds as to their oxidative stress potential in rat liver. In addition to a role for microarrays in predictive toxicology, analyses of small subsets of these signature profiles, genes within a specific pathway, or even single genes often provide important insights into possible mechanisms involved in the toxicities of these compounds.
Keywords
Related Topics
Life Sciences
Environmental Science
Health, Toxicology and Mutagenesis
Authors
Michael McMillian, Alex Nie, J. Brandon Parker, Angelique Leone, Michael Kemmerer, Stewart Bryant, Judy Herlich, Lynn Yieh, Anton Bittner, Xuejun Liu, Jackson Wan, Mark D. Johnson, Peter Lord,