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Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure.
Citation:
ROYLAND, J. E., PRASADA RAO S. KODAVANTI, G. W. KNAPP, AND R. C. MACPHAIL. Use of a custom RT-PCR array to analyze toxicity pathways at different life stages in Brown Norway Rat Brain following acute Toluene exposure. Presented at Society of Toxicology (SOT) Annual Meeting, Washington, DC, March 06 - 10, 2011.
Impact/Purpose:
To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norway rats at 4, 12 and 24 months of age.
Description:
To investigate the contribution of different life stages on response to toxicants, we utilized a custom designed RT-PCR array to examine the effects of acute exposure by oral gavage of the volatile organic solvent toluene (0.00, 0.65 or 1.0 glkg) in the brains of ma1e Brown Norway rats at 4, 12 and 24 months of age. Toluene is a known neurotoxicant with effects on cognition, motor activity and neurotransmitters in the central nervous system. The objective was to explore the toxicity pathways that contribute to the adverse effects of toluene exposure, and to determine if the response is age-dependent. In this study, we examined gene expression in cerebellum, striatum, hippocampus and frontal cortex 4 hours postdosing using a custom designed RT-PCR array containing 30 genes representing key toxicity pathways involving energy metabolism, oxidative stress, neuronal plasticity, immune and stress responses. Results showed that the effect of age exceeded that of toluene on number of genes affected (approx 2 to 5x depending on brain area). With the exception of toluene effect in striatum, percent of up regulation (averaged ~80% with age and near 100% with toluene) exceeded that of down regulation in this subset of genes selected as possible markers of susceptibility. Based on number of genes affected, cerebellum displayed the greatest sensitivity. However, based on direction of expression changes, striatum was most vulnerable. These data indicate that response to toxicant exposure is impacted by life stage, which, in itself, affects gene expression levels. Data also indicate variability in response across brain areas, with degree and direction of change depending upon condition tested. These ongoing studies contribute to defining a genomic model of toxicity pathways in the nervous system and their modification with aging. (This abstract does not necessarily reflect USEPA policy).