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Toxicogenomic effects of sub-lethal exposures of organophosphates on mouse liver cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): synthetic construct Mus musculus

PROVIDER: GSE78225 | GEO | 2016/02/24

SECONDARY ACCESSION(S): PRJNA312951

REPOSITORIES: GEO

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Toxicogenomic effects of sub-lethal exposures of organophosphates on mouse liver cells

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-02-24 | E-GEOD-78225 | biostudies-arrayexpress

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

Project description: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.

2016-02-24 | GSE78223 | GEO

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

2016-02-24 | GSE78222 | GEO

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

Project description:In order to examine the long term effects of the OPs, murine liver cells (BNL CL.2, ATCCÂ® 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. Three biological replicates of ;iver cells were exposed to three representative OPs and then harvested at three time points (2 hours, 72 hours, and two weeks) following exposure. These time points were designed for a determination of both early and late effects as well as identification of persistent, chronic changes. The RNAs from the collected cells were extracted and processed on commercial microarrays to determine the gene expression patterns and miRNA profiles associated with response to exposure to the OPs.

2016-02-24 | E-GEOD-78223 | biostudies-arrayexpress

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

Project description:In order to examine the long term effects of the OPs, murine liver cells (BNL CL.2, ATCCÂ® 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. Three biological replicates of liver cells were exposed to three representative OPs and then harvested at three time points (2 hours, 72 hours, and two weeks) following exposure. These time points were designed for a determination of both early and late effects as well as identification of persistent, chronic changes. The RNAs from the collected cells were extracted and processed on commercial microarrays to determine the gene expression patterns and miRNA profiles associated with response to exposure to the OPs.

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Toxicogenomic effects of marine brevetoxins in liver and brain of mouse.

Project description:Although the polyether brevetoxins (PbTx's) produced by Karenia brevis (the organism responsible for blooms of the Florida red tide) are known to exert their acute toxic effects through ion-channel mediated pathways in neural tissue, prior studies have also demonstrated that at least one form of the toxin (PbTx-6) is bound avidly by the aryl hydrocarbon receptor (AhR). Since AhR binding of a prototypical ligand such as dioxin is the first step in a cascade pathway producing major changes in gene expression, we reasoned that PbTx-6 might produce similar genomic-wide changes in expression. Mice were injected i.p. with sub-lethal doses of PbTx's (either 1.5 or 3 mg/g body weight of PbTx-6; or 0.15 mg/g body weight of PbTx-2, a toxin not avidly bound by the AhR), and liver and brain tissues were sampled at 8, 24 and 72 h and RNA was isolated. Changes in gene-specific RNA levels were assessed using commercially available mouse cDNA arrays (Incyte) containing >9600 array elements, including many elements from AhR-mediated genes. Histopathology of the two organs was also assessed. We observed minor histopathological effects and a total of only 29 significant (>2.0-fold) changes in gene expression, most of which occurred in the liver, and most of which could be attributable to an 'acute phase' inflammatory response. These results argue against the hypothesis that PbTx-6 acts via a classic AhR-mediated mechanism to evoke gene expression changes. However, given the avidity with which PbTx-6 binds to the AhR, these findings have important implications for how PbTx's may act in concert with other toxicants that are sensed by the AhR.

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Comparative analysis of the toxicogenomic effects of Ortho-Benzyl-Para-ChloroPhenol (OBPCP) and Para-Tertiary AmylPhenol (PTAP) on Staphylococcus aureus

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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