| Sign In to gain access to subscriptions and/or personal tools. |
DOI: 10.1080/01926230701311351 © 2007 Society of Toxicologic Pathology Genomic Profiling in Nuclear Receptor-Mediated ToxicityDepartment of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA
Department of Veterinary and Biomedical Sciences and Center for Molecular Toxicology and Carcinogenesis, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, North Carolina 27599, USA, iir{at}unc.edu Nuclear receptors (NRs) are attractive drug targets due to their role in regulation of a wide range of physiologic responses. In addition to providing therapeutic value, many pharmaceutical agents along with environmental chemicals are ligands for NRs and can cause adverse health effects that are directly related to activation of NRs. Identifying the molecular events that produce a toxic response may be confounded by the fact that there is a significant overlap in the biological processes that NRs regulate. Microarrays and other methods for gene expression profiling have served as useful, sensitive tools for discerning the mechanisms by which therapeutics and environmental chemicals invoke toxic effects. The capability to probe thousands of genes simultaneously has made genomics a prime technology for identifying drug targets, biomarkers of exposure/toxicity and key players in the mechanisms of disease. The complex intertwining networks regulated by NRs are hard to probe comprehensively without global approaches and genomics has become a key technology that facilitates our understanding of NR-dependent and -independent events. The future of drug discovery, design and optimization, and risk assessment of chemical toxicants that activate NRs will inevitably involve genomic profiling. This review will focus on genomics studies related to PPAR, CAR, PXR, RXR, LXR, FXR, and AHR.
Key Words: Toxicogenomics nuclear receptor transcription profiling PPAR CAR PXR AHR.
|
