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USING ARRAY TECHNOLOGY TO IDENTIFY POTENTIAL BIOMARKERS FOR PYRETHROID INSECTICIDES.
Citation:
Harrill, J., M. J. Wolansky, S D. Hester, J M. Hedge, AND K M. Crofton. USING ARRAY TECHNOLOGY TO IDENTIFY POTENTIAL BIOMARKERS FOR PYRETHROID INSECTICIDES. Presented at Society of Toxicology, New Orleans, LA, March 06 - 10, 2005.
Description:
Pyrethroid insecticides affect nervous system function by disruption of sodium channels in nerve membranes. FQPA requirements for assessing cumulative risk have increased the need for rapid and sensitive biomarkers of effect. This project aims to develop biochemical markers of neurotoxicity following acute exposure to pyrethroids. Gene arrays were used to determine candidate proteins to serve as biomarkers. Male rats were orally exposed to deltamethrin (1-6 mg/kg, DLT) or permethrin (50-200 mg/kg, PER) in corn oil vehicle. Tissue was collected at 2, 6, or 24 hr after exposure. Total RNA was isolated from whole brain or frontal cortex. RNA was analyzed using either ClonTech Rat Tox 1.2 arrays (whole brain) or Affymetrix Rat 230 2.0 arrays (frontal cortex). Data analyses revealed relatively few genes that were altered in both PER and DLT treated tissue. For PER, 115 transcripts responded in a dose-related manner (including at least a 3-fold increase at highest dose). For DLT, 126 genes responded in a dose-related manner. From these two sets, 13 transcripts were identified as responding similarly for both pyrethroids, including 7 genes with known identities: e.g. carboxylesterase 1, recoverin, phenylalanine hydroxylase, leucyl-specific aminopeptidase PILS. For DLT treatment using the ClonTech Rat Tox 1.2 array, 29 genes responded in a dose-dependent manners. Of the 13 transcripts common to the two pyrethroids in the Affymetrix array, 2 were up-regulated >3-fold in the ClonTech Rat Tox 1.2 array with the same dose of DLT at 24 hours. These differences may be due to the use of frontal cortex versus whole brain or variation in treatment times. Future work will involve confirming candidate genes from both technologies using qRT-PCR or protein activity assays. (This is abstract does not necessarily reflect USEPA policy)