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ANALYSIS OF TOLUENE AT DIFFERENT LIFE STAGES IN BROWN NORWAY RATS.
ROYLAND, J. E. ANALYSIS OF TOLUENE AT DIFFERENT LIFE STAGES IN BROWN NORWAY RATS. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
In this study global genomic changes were examined after acute oral toluene exposures at 3 ages in Brown Norway Rats.
Differential susceptibility to environmental exposures in subsets of the population is a major regulatory concern of the Environmental Protection Agency. Of special interest is the elderly, the fastest growing segment of the population who may be considered a special at risk group because of physiological changes in sensitivity, elimination, homeostatic and/or repair mechanisms. In this study global genomic changes (Affymetrix rat 230A chips) were examined after acute oral toluene exposures (0, 650 and 1000 mg/kg) at 3 ages (4, 12 and 24 mos) in Brown Norway Rats (4 animals/gp; 36 arrays total). Hippocampi were dissected out 4 hrs after exposure, gene expression determined and data analyzed across age and dose groups to identify response to toluene and the effect age has on that response. Two-way ANOVA (p < 0.05) identified 1418 genes differentially expressed with age across any treatment group, 206 genes changed with dose, and 198 genes through an interaction between the two parameters indicating that the impact of age alone is much greater than the effect of acute toluene exposures. However, the data also show, as indicated by the number of genes displaying an age/dose interaction, that life stage can impact toxic response. Further analysis to identify the genes that differed between groups documented 595 genes that changed between 4 and 12 mos of age and 610 genes between 12 and 24 mos with 127 of those genes differing across all 3 age groups. Similar analysis of genes that changed with dose found 53 genes that were different between the 650 and 0 mg/kg toluene groups, 73 genes between the 1000 and 650 mg/kg doses and 10 genes that were in common across doses. Expression of genes with roles in immune response (up-regulated) or cytoskeleton, protein metabolism and energy metabolism (all down-regulated) were changed as life stage progressed, indicating changes in basic cell homeostasis. These data will help identify processes for further investigation into the role of aging in susceptibility.