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AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE
Citation:
ROYLAND, J. E., U. P. KODAVANTI, AND R. C. MACPHAIL. AGE-RELATED TOXICITY PATHWAY ANALYSIS IN BROWN NORWAY RAT BRAIN FOLLOWING ACUTE TOLUENE EXPOSURE. Presented at Keystone Symposia: Biomolecular Interaction Networks: Function and Disease, Quebec, QC, CANADA, March 07 - 12, 2010.
Impact/Purpose:
The objective was to explore the toxicity pathways that contribute to the mode of action(s) causing the adverse effects of toluene exposure, and to determine If the response is age-dependent
Description:
The influence of aging on susceptibility to environmental exposures is poorly understood. To investigate-the contribution of different life stages on response to toxicants, we examined the effects of an acute exposure to the volatile organic compound, toluene (0.0 or 1.0 g/kg), in the brains of Brown Norway rats at 4 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 is to explore the toxicity pathways that contribute to the mode of action(s) causing the adverse effects of toluene exposure, and to determine if the response is age-dependent. In this initial study we examined gene expression in cerebellum 4 hours post-dosing using commercial RT-PCR arrays containing 84 key genes representing multiple toxicity pathways, plus housekeeping genes and control wells. Data show that the effect of age is greater than the effect of toluene on number of genes affected (approx 1.5 times more with age). Numbers of up-and down-regulated genes were about the same due to age (4 vs. 24 month controls), but, within an age group, more were up-than down-regulated due to toluene exposure (approx. 70% up). However, when comparing age-related toluene effects (4 vs. 24 months treated) more genes were down-than up-regulated (approx. 65% down). These data indicate that life stage alone affects gene expression levels and can impact the response to toxicant exposure at the molecular level. Affected genes are associated with stress-, survival-and growthrelated pathways with degree and direction of change variable, depending upon condition tested (E.g. 4 month control vs. 24 month control or 4 month control vs. 4 month treated). These ongoing studies contribute to defining a genomic model of toxicity pathways and show how aging affects toxic response. (This abstract does not necessarily reflect USEPA policy}.