You are here:
CHANGES IN MRNA EXPRESSION PROFILES IN RAT CORTEX AND STRIATUM FOLLOWING SUB CHRONIC TOLUENE EXPOSURE.
Citation:
JOHNSTONE, A. F., S. D. HESTER, W. K. BOYES, P. J. BUSHNELL, C. MEACHAM, AND T. J. SHAFER. CHANGES IN MRNA EXPRESSION PROFILES IN RAT CORTEX AND STRIATUM FOLLOWING SUB CHRONIC TOLUENE EXPOSURE. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
A genomic approach was used to identify possible molecular and genomic mechanisms of neurotoxic effects following sub-chronic toluene exposure.
Description:
Toluene, a volatile organic compound (VOC) used in many commercial products, is a ubiquitous air pollutant and therefore of interest to many EPA regulatory programs. A primary concern for toluene and other VOC’s is the potential for persistent neurotoxic effects from long term exposure. While the acute actions of these chemicals have been studied extensively, little is known about the possible mechanisms by which VOC’s may cause long-term effects on the CNS. Thus, a genomic approach was used to identify possible molecular and genomic mechanisms of neurotoxic effects following sub-chronic toluene exposure. Long-Evans rats were exposed to toluene via inhalation (0, 10, 100, 1000 ppm, n = 5 for each dose), 6 hrs/day, 5 d/wk for 13 weeks. The day following the final exposure, total mRNA was extracted from the cerebral cortex (CTX) and striatum (STR) and hybridized to high density Rat 230A Affymetric arrays. Changes in mRNA expression levels were analyzed in each tissue using two-way ANOVA with a false discovery rate of 0.05 to assess differential gene expressions. Analysis showed the number of significant genes as follows: 6995, 215 and 154 for tissue, dose and tissue/dose interaction, respectively. Principle component analysis showed separation between the control and 1000 ppm group in CTX, and a threshold in STR where control and 10 ppm were distinguishable from 100 and 1000 ppm. Thus, sub-chronic toluene exposure caused tissue and dose-dependent changes in mRNA expression. The present results may provide information regarding mechanisms underlying sub-chronic toluene neurotoxicity.