Toxicogenomic effects of sub-lethal exposures of organophosphates on mouse liver cells [mRNA Expression]

In order to examine the long term effects of the OPs, murine liver cells (BNL CL.2, ATCC TIB-73) have been exposed to sub-lethal doses of three OPs: diisopropylfluorophosphate (DFP) representative of sarin and soman, O,S-diethyl methylphosphonothioate (OSD) serving as a simulant for VX, and paraoxon as an example of OP insecticides. Dosing levels of these compounds was set at 20% of the IV LD50 for each, with a 4 hour exposure time. Gene arrays and physiological tests were run at three time points following exposure; 2 hours, 2 days, and 2 weeks. The physiological results showed little to no effect upon exposure to sub-lethal dose of OPs. Gene expression and microRNA (miRNA) profiles using GeneChip Mouse Gene 1.0 ST arrays and miRNA arrays (Affymetrix, Santa Clara, CA) found that the OPs did alter expression of genes related to several systems previously implicated in OP exposure with no long term effects. In addition, a significant number of sRNA/snRNA and ribosomal RNA were found to be affected suggesting the need for further study of the changes in these regulators.

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