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PYRETHROID INDUCED ALTERATIONS IN TRANSCRIPTION OF CALCIUM RESPONSIVE AND IMMEDIATE EARLY GENES IN VIVO.
Citation:
HARRILL, J. AND K. M. CROFTON. PYRETHROID INDUCED ALTERATIONS IN TRANSCRIPTION OF CALCIUM RESPONSIVE AND IMMEDIATE EARLY GENES IN VIVO. Presented at Society of Toxicology, San Diego, CA, March 05 - 09, 2006.
Description:
Multiple molecular targets for pyrethroid insecticides have been evaluated in in vitro preparations, including but not limited to voltage-sensitive sodium channels (VSSCs), voltage-sensitive calcium channels (VSCCs), GABAergic receptors, ATPases and mitochondrial respiratory chain complexes. However, little information exists concerning alterations in downstream biochemical and cellular pathways that result from pyrethroid interactions at these targets. Acute oral dose-response studies for permethrin (PERM, Type I: 1.0–100 mg/kg) and deltamethrin (DLT, Type II: 0.3 – 3.0 mg/kg) were performed using adult, male Long-Evans rats. Cortical tissue was collected at 6 hr and global transcriptional alterations were assessed with Affymetrix GeneChip® oligonucleotide microarrays. Microarray analysis identified alterations in a large number of transcripts. Specifically, transcription of Ca+2/calmodulin dependent protein kinase Ig (CamkIg) is induced by DLT and PERM in a dose-dependent manner (as identified by microarray analysis and confirmed for DLT by qRT-PCR in a second cohort of animals). Microarray and qRT-PCR data demonstrate that CamkIIa, CamkIIb and CamIV transcription was not altered by DLT exposure. Microarray analysis also identified several immediate early genes (such as c-fos and Arc) with reduced expression at 6 hr following DLT and PERM exposure. A qRT-PCR time course study with DLT (3.0 mg/kg at 3,6,9,12 and 24 hr) confirmed upregulation of CamkIg with a peak at 6 hr. There was a 2-4-fold induction of expression of c-fos, Arc, and JunB at 3 hr, prior to a decrease observed at 6 hr. Early upregulation of these immediate early genes may inform the identity of other downstream transcriptional events. In summary, DLT exposure alters the expression of CamkIg as well as several immediate early genes. (This abstract does not reflect U.S. EPA policy.)