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TOXICOGENOMIC ANALYSIS OF TOLUENE EXPOSURE AT 3 AGES IN BROWN NORWAY RATS.
ROYLAND, J. E. TOXICOGENOMIC ANALYSIS OF TOLUENE EXPOSURE AT 3 AGES IN BROWN NORWAY RATS. Presented at American Aging Association, San Antonio, TX, June 01 - 04, 2007.
A major concern in assessing toxicity to environmental exposures is differential
susceptibility in subsets of the population. Aging adults, who comprise the fastest
growing segment of the population, may possess a greater sensitivity due to changes in
metabolic, reserve and repair capacities. However, little data exists on the risks to older
individuals. Our goal is to identify factors that contribute to increased susceptibility in
the aged. Brown Norway Rats, ages 4, 12 and 24 mos., were orally dosed with Toluene
(0, 650 or 1000 mg/kg) and hippocampi dissected out after 4 hrs exposure. Global gene
expression was determined on Affymetrix rat 230A chips (4 animals/gp, 36 arrays total).
Data are analyzed across age and dose groups to identify patterns of genomic response to
toluene and the effect age has on that response. ANOVA (p < .05) identified 168 genes
differentially expressed between any dose at 4 mos of age, 21 3 genes at 12 mos and 121
genes at 24 mos. Similar analysis across ages found 357 genes differentially expressed at
0 mg/kg toluene, 369 genes at the 650 mg/kg dose and 392 genes at 1000 mg/kg. Genes
differentially expressed between any age/dose were filtered on fold change (1.25x) for
further analysis. GO gene ontology shows that in 4 month animals, toluene up-regulates
genes with roles in amino acid synthesis and regulation of cellular processes while down-
regulating those involved in extra cellular matrix and cell adhesion. In animals 12 and 24
mos old, genes involved in cell migration and nucleotide metabolism, respectively, are
highly represented. These data help identify processes for further investigation into the
role of aging in susceptibility. (This abstract does not necessarily reflect USEPA policy).