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TIME COURSE OF THE TRANSCRIPTIONAL RESPONSE OF RAT CEREBROCORTICAL TISSUE AFTER ACUTE IN VIVO PYRETHROID EXPOSURE.
Citation:
HARRILL, J., F. A. WRIGHT, AND K. M. CROFTON. TIME COURSE OF THE TRANSCRIPTIONAL RESPONSE OF RAT CEREBROCORTICAL TISSUE AFTER ACUTE IN VIVO PYRETHROID EXPOSURE. Presented at Society of Toxicology, Seattle, WA, March 16 - 20, 2008.
Impact/Purpose:
This study tests the hypothesis that acute exposure to equipotent doses of Type I and Type II pyrethroids induce similar transcriptional alterations in cerebrocortical tissue.
Description:
Pyrethroid insecticides disrupt neuronal function by interfering with the function of voltage-sensitive Na+ channels (VSSCs). Distinct differences in the pharmacological actions of pyrethroid sub-types (Type I or Type II) on VSSCs have been observed. The impact of these pharmacological actions on downstream, intracellular signaling pathways has not been fully explored, nor is it clear whether similar pathways are targeted by different pyrethroid sub-types. This study tests the hypothesis that acute exposure to equipotent doses of Type I and Type II pyrethroids induce similar transcriptional alterations in cerebrocortical tissue. Our goals are identification of biochemical markers of effect for the pyrethroids and comparison of effects across pyrethroid sub-types. Long-Evans rats were acutely exposed (p.o) to equipotent doses (ED30 for motor activity) of: deltamethrin (DLT), cypermethrin (CYP), cyfluthrin (CYF), permethrin (PERM), bifenthrin (BIF) or tefluthrin (TEF) (3, 10.7, 2.3, 43, 3.2 and 2.3 mg/kg, respectively, n=6/group). Tissue was collected at 3 or 6 h post-exposure. Vehicle controls were collected at each time point (n = 12/group). Affymetrix Rat 230 2.0 GeneChips® were used to obtain transcriptional profiles. Two statistical methods, Linear Models for Microarray Data (limma) and two-way ANOVA with Benjamini-Hochberg multiple testing correction, were used to identify treatment related effects within each test compound. Expression of a number probe sets were altered for the Type II pyrethroids (DLT, CYP & CYF) with both the limma (102, 82 & 127, respectively) and ANOVA (238, 73 & 124, respectively) methods. A large degree overlap in the altered probe sets was observed between Type II pyrethroids. No significant alterations in transcript expression were observed for the Type I pyrethroids (PERM, BIF & TEF) at these dose levels with either method. Several immediate early genes and glucocorticoid-receptor mediated transcripts were altered for the type II’s. These data indicate that equipotent low-dose acute exposures to Type I and Type II pyrethroids do not produce equivalent genomic responses in rat cerebrocortical tissue.