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GENE EXPRESSION PROFILING OF ACCESSIBLE SURROGATE TISSUES TO MONITOR MOLECULAR CHANGES IN INACCESSIBLE TARGET TISSUES FOLLOWING TOXICANT EXPOSURE
Citation:
Rockett, J C., C. BLYSTONE, A. GOETZ, R. MURRELL, AND D. J. DIX. GENE EXPRESSION PROFILING OF ACCESSIBLE SURROGATE TISSUES TO MONITOR MOLECULAR CHANGES IN INACCESSIBLE TARGET TISSUES FOLLOWING TOXICANT EXPOSURE. Presented at Society of Toxicology, Salt Lake City, UT, March 09 - 13, 2003.
Description:
Gene Expression Profiling Of Accessible Surrogate Tissues To Monitor Molecular Changes In Inaccessible Target Tissues Following Toxicant Exposure
John C. Rockett, Chad R. Blystone, Amber K. Goetz, Rachel N. Murrell, Judith E. Schmid and David J. Dix
Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Gene expression profiling (GEP) offers the potential to classify toxicant exposures, predict clinical outcome of such exposures, and provide mechanistic data useful for risk assessments. It could ultimately provide a vehicle for developing early diagnostic and preventative measures in at-risk populations or individuals. However, using GEP to monitor the impact of toxicant exposures on inaccessible tissues is a difficult prospect, since direct biopsy of such tissues is not feasible. A less invasive method must therefore be developed. We propose that gene expression changes in accessible (surrogate) tissues (e.g. blood) often reflect those in inaccessible (target) tissues, thus offering a convenient biomonitoring method to provide insight into the effects of environmental toxicants on target tissues. GEP of surrogate and target tissues have been compared following exposure of animal models to model compounds and environmental toxicants. In an initial pilot study, gene expression changes in peripheral blood lymphocytes (PBLs) were compared to those in the uteri of adult rats to identify genes that were altered in both tissues following estradiol treatment. Ovariectomized rats were treated with either 17-b-estradiol or vehicle control for 3 days. PBL and uterine RNAs were hybridized to arrays containing 1185 genes. A number of genes (e.g. jun-D, phospholipase A2, thymidine kinase) were found to demonstrate a similar degree of expression change that was treatment-, but not tissue-specific. This indicates that accessible tissues such as PBLs can serve as surrogate tissues for observing gene expression changes in the uterus following chemical exposure, and provides supportive evidence for the surrogate tissue analysis concept. This presentation will also discuss data from a follow-up study, currently in progress, in which GEP of a variety of surrogate and target tissues is being conducted in rodent models exposed to conazoles. This is an abstract of a proposed presentation and does not necessarily reflect EPA policy.