Transcription profiling of rat liver or brain cortex exposured to the explosive rexahydro-1,3,5-trinitro-1,3,5-triazine - RDX (3mg/kg or 18mg/kg; 0, 4, 24, 48 hr)
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: James Dillman
PROVIDER: E-GEOD-12196 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:RDX (Hexahydro-1,3,5-trinitro-1,3,5-triazine) is a synthetic, high-impact, relatively stable explosive that has been in use since WWII. Exposure to RDX can occur either occupationally or through ordnance that lays unexploded on training ranges. The toxicology of RDX is dominated by acute tonic-clonic seizures at high doses, which remit when exposure is removed and internal RDX levels decrease. Sub-chronic studies have revealed few other toxic effects. The objective of this study was to examine the effect of a single oral dose of RDX on global gene expression in the mammalian brain and liver, using a rodent model. Keywords: time course, dose response
2009-03-13 | GSE12196 | GEO
Project description:Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (M-bM-^IM-$ 17), indicating that 2,6-DNT exposure had relatively little impact on the brain in comparison to RDX. Birds exhibiting RDX-induced seizures accumulated over 20M-CM-^W more RDX in brain tissues in comparison to non-seizing birds even within a common dose. In parallel, expression patterns were unrelated among seizing and non-seizing birds exposed to equivalent RDX doses. In birds experiencing seizures, genes related to neuronal electrophysiology and signal transduction were significantly affected. Comparative toxicology revealed strong similarity in acute exposure effects between RDX and the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) regarding both molecular mechanisms and putative mode of action. In a manner similar to DDT, we hypothesize that RDX elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms. Northern Bobwhite 14 Day RDX High Dose Exposure, Brain Tissue Investigation (High Laser Intensity Scan): Juvenile male and female Northern bobwhite (12 weeks of age) were dosed with RDX by daily gavage (0, 20, 80, 125, or 180 mg/kg/day). Each treatment group included seven birds (at least three of each sex per treatment). All RDX doses in the 14-day high-dose experiment elicited seizures within 3 days of experiment initiation (Johnson et al., 2007). Microarray experiments were conducted using a balanced interwoven-loop design using Cyanine-3 (Cy3) and A647. This experiment investigated the 14-day RDX high-dose exposure. All RDX-dosed quail accumulated ~20 mg/kg RDX in brain tissues (Johnson et al., 2007) and exhibited seizures. Transcript expression was compared among three male and three female controls versus three male and three female RDX-seized quail incorporating two dye swaps per biological replicate totaling 24 microarrays. Hybridizations included four technical replicates and two dye swaps per biological replicate resulting in a total of 24 micorarrays assayed. To broaden signal detection, each microarray was scanned at high and low laser power to resolve low-intensity spots and reduce signal saturation, respectively (Skibbe et al., 2006). This dataset represents the High Intensity Scan.
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Project description:ABSTRACT: The central nervous system is remarkably plastic in its ability to recover from trauma. We examined recovery from hexahydro-1,3,5-trinitrotriazine (RDX) induced seizures in rat through changes in transcriptional networks. Transcriptional networks from time series experiments provide a good basis for organizing and studying the dynamic behavior of biological processes. The goal of this work was to identify networks affected by chemical exposure and track changes in these networks as animals recover. We examined brain microarray data from rats exposed to 0, 1.2, 12, 24, and 47 mg RDX/kg body weight at different time points after exposure (24hr, 48hr, 7d, 14d, 28d and 90d). RESULTS A credible transcriptional network was constructed from the gene expression microarray data, which predicts the role of some key genes such as heat shock proteins, neuropeptide Y, thyrotropin-releasing hormones, growth factors, and ion channels in neurotransmission and neuroprotective mechanisms. Examination of the dynamic changes in expression within this network over time provided insight into CNS protective mechanisms from traumas. Single RDX Exposure with Various Time Points, Brain Tissue Investigation: Sprague-Dawley female rats were exposed to a single oral gavage of one of four concentrations of RDX or vehicle control with sampling periods of 24h, 48h, 7d, 14d, 28d, or 90d. Brain tissue was investigated for differential expression in response to RDX exposure and provide insight into CNS protective mechanisms associated with RDX exposure.
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Project description:Roots transcriptome responses 14-day old Arabidopsis seedlings grown submerged in MS medium and exposed to TNT or RDX. Keywords = phytoremediation Keywords = explosives Keywords = TNT Keywords = RDX Keywords: parallel sample Complete experiment contains only three samples, including the control.
2003-07-30 | E-GEOD-560 | biostudies-arrayexpress
Project description:Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (M-bM-^IM-$ 17), indicating that 2,6-DNT exposure had relatively little impact on the brain in comparison to RDX. Birds exhibiting RDX-induced seizures accumulated over 20M-CM-^W more RDX in brain tissues in comparison to non-seizing birds even within a common dose. In parallel, expression patterns were unrelated among seizing and non-seizing birds exposed to equivalent RDX doses. In birds experiencing seizures, genes related to neuronal electrophysiology and signal transduction were significantly affected. Comparative toxicology revealed strong similarity in acute exposure effects between RDX and the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) regarding both molecular mechanisms and putative mode of action. In a manner similar to DDT, we hypothesize that RDX elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms. Female Northern Bobwhite 14 Day 2,6-DNT Exposure, Brain Tissue Investigation (Low Laser Intensity Scan): Juvenile female Northern bobwhite (12 weeks of age) were dosed with 2,6-DNT by daily gavage (0, 50, 100, 190, or 350 mg/kg/day). Each treatment group included seven birds (at least three of each sex per treatment). Microarray experiments were conducted using an interwoven-loop design using Cyanine-3 (Cy3) and A647. This experiment investigated the effects of the 14-day 2,6-DNT exposure in females including controls, 60, and 100 mg/kg/day treatments, each including 3 biological replicates. To broaden signal detection, each microarray was scanned at high and low laser power to resolve low-intensity spots and reduce signal saturation, respectively (Skibbe et al., 2006). This dataset represents the Low Intensity Scan.
2011-11-22 | E-GEOD-33888 | biostudies-arrayexpress
Project description:Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (M-bM-^IM-$ 17), indicating that 2,6-DNT exposure had relatively little impact on the brain in comparison to RDX. Birds exhibiting RDX-induced seizures accumulated over 20M-CM-^W more RDX in brain tissues in comparison to non-seizing birds even within a common dose. In parallel, expression patterns were unrelated among seizing and non-seizing birds exposed to equivalent RDX doses. In birds experiencing seizures, genes related to neuronal electrophysiology and signal transduction were significantly affected. Comparative toxicology revealed strong similarity in acute exposure effects between RDX and the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) regarding both molecular mechanisms and putative mode of action. In a manner similar to DDT, we hypothesize that RDX elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms. Female Northern Bobwhite 14 Day 2,6-DNT Exposure, Brain Tissue Investigation (High Laser Intensity Scan): Juvenile female Northern bobwhite (12 weeks of age) were dosed with 2,6-DNT by daily gavage (0, 50, 100, 190, or 350 mg/kg/day). Each treatment group included seven birds (at least three of each sex per treatment). Microarray experiments were conducted using an interwoven-loop design using Cyanine-3 (Cy3) and A647. This experiment investigated the effects of the 14-day 2,6-DNT exposure in females including controls, 60, and 100 mg/kg/day treatments, each including 3 biological replicates. To broaden signal detection, each microarray was scanned at high and low laser power to resolve low-intensity spots and reduce signal saturation, respectively (Skibbe et al., 2006). This dataset represents the High Intensity Scan.
2011-11-22 | E-GEOD-33893 | biostudies-arrayexpress
Project description:Naval training exercises involving live ordnance can introduce munitions constituents (MCs) such as 1,3,5-trinitro-1,3,5 triazine (RDX) into the marine environment posing a potential environmental hazard to reef organisms, including corals. We developed a bioinformatic infrastructure and high-density microarray for a coral consortium and assessed the effects of RDX bioaccumulation on gene expression related to coral and endosymbiont health in the reef building coral (Acropora formosa). High-throughput sequencing and assembly of the transcriptomes for A. formosa and all eukaryotic endosymbionts yielded 189,616 unique sequences and 25,003 significant functional matches to protein-coding genes. Functional annotation and metabolic pathway associations were also developed. The bioinformatics base was transitioned to custom 15,000 probe microarrays that were used to assess RDX effects on gene expression in the A. formosa coral consortium. Coral fragments were exposed to RDX (0.5, 1, 2, 4, and 8 mg/L) for 5d in a controlled laboratory experiment. RDX readily accumulated into coral tissues; however, bioconcentration was minimal (bioconcentration factor = 1.09-1.50). RDX caused no significant changes in zooxanthellae tissue densities, however a significant (p<0.05) 40% increase in mucocytes was observed in the 8 mg/L exposure indicating a mucosal protective response to RDX exposure. Investigation of T-RFLP profiles indicated significant differences in bacterial community composition inhabiting the coral surface microlayer of Acropora sp. between control and RDX-exposed coral as among exposure concentrations. Differential expression of transcripts increased with increasing RDX concentration where 126, 195 and 272 transcripts were differentially expressed in the 0.5, 2.0 and 8 mg/L RDX treatments, respectively. The commonality in differentially expressed transcripts (DET) among exposure concentrations ranged from 9.9 to 29.0% where the lowest commonality was observed between the most disparate RDX exposure concentrations. Increasing RDX concentrations caused an increasing proportion of the number of transcripts differentially expressed in symbionts relative to corals. Further, a trend toward decreased transcript expression in symbionts in response to increasing RDX concentration was observed where 20.0% of differentially expressed transcripts had decreased expression at the 0.5 mg/L concentration, whereas 80.4% had decreased expression at the 8 mg/L concentration. Investigation of KEGG orthology for DET indicated potential impacts of RDX on a variety of molecular pathways, predominantly in endosymbionts compared to the coral host. Prominent effects of RDX exposure on pathways included enrichment of DET involved in carbohydrate metabolism, amino acid metabolism, energy metabolism, lipid metabolism, metabolism of cofactors and vitamins, environmental information processing and cellular processes. Fragments of the living branched coral Acropora formosa were obtained from Oceans, Reefs and Aquaria (http://www.orafarm.com). Ten gallon aquaria were used to expose 5 coral fragments to control or RDX exposure conditions (0.49, 0.93, 1.77, 3.67 and 7.18 mg/L, measured concentrations). The microarray hybridization experiment included 3 biological replicates for the 0.5, 2, and 8 mg/L RDX conditions and 4 biological replicates for the control.
2014-03-26 | E-GEOD-27624 | biostudies-arrayexpress
Project description:Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (M-bM-^IM-$ 17), indicating that 2,6-DNT exposure had relatively little impact on the brain in comparison to RDX. Birds exhibiting RDX-induced seizures accumulated over 20M-CM-^W more RDX in brain tissues in comparison to non-seizing birds even within a common dose. In parallel, expression patterns were unrelated among seizing and non-seizing birds exposed to equivalent RDX doses. In birds experiencing seizures, genes related to neuronal electrophysiology and signal transduction were significantly affected. Comparative toxicology revealed strong similarity in acute exposure effects between RDX and the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) regarding both molecular mechanisms and putative mode of action. In a manner similar to DDT, we hypothesize that RDX elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms. Male Northern Bobwhite 14 Day 2,6-DNT Exposure, Brain Tissue Investigation (Low Laser Intensity Scan): Juvenile male and female Northern bobwhite (12 weeks of age) were dosed with 2,6-DNT by daily gavage (0, 50, 100, 190, or 350 mg/kg/day). Each treatment group included seven birds (at least three of each sex per treatment). This microarray data set represents investigation of the male birds. Microarray experiments were conducted using an interwoven-loop design using Cyanine-3 (Cy3) and A647. This experiment investigated the effects of the 14-day 2,6-DNT exposure in males including controls and 60 mg/kg/day treatments, each including 3 biological replicates. To broaden signal detection, each microarray was scanned at high and low laser power to resolve low-intensity spots and reduce signal saturation, respectively (Skibbe et al., 2006). This dataset represents the Low Intensity Scan.
2011-11-23 | E-GEOD-33934 | biostudies-arrayexpress
Project description:Munitions constituents (MCs) including hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 2,4,6-trinitrotoluene (TNT), and TNT derivatives are recognized to elicit aberrant neuromuscular responses in many species. The onset of seizures resulting in death was observed in the avian model Northern bobwhite after oral dosing with RDX beginning at 8 mg/kg/day in subacute (14 days) exposures, whereas affective doses of the TNT derivative, 2,6-dinitrotoluene (2,6-DNT), caused gastrointestinal impacts, lethargy, and emaciation in subacute and subchronic (60 days) exposures. To assess and contrast the potential neurotoxicogenomic effects of these MCs, a Northern bobwhite microarray was developed consisting of 4119 complementary DNA (cDNA) features enriched for differentially-expressed brain transcripts from exposures to RDX and 2,6-DNT. RDX affected hundreds of genes in brain tissue, whereas 2,6-DNT affected few (M-bM-^IM-$ 17), indicating that 2,6-DNT exposure had relatively little impact on the brain in comparison to RDX. Birds exhibiting RDX-induced seizures accumulated over 20M-CM-^W more RDX in brain tissues in comparison to non-seizing birds even within a common dose. In parallel, expression patterns were unrelated among seizing and non-seizing birds exposed to equivalent RDX doses. In birds experiencing seizures, genes related to neuronal electrophysiology and signal transduction were significantly affected. Comparative toxicology revealed strong similarity in acute exposure effects between RDX and the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT) regarding both molecular mechanisms and putative mode of action. In a manner similar to DDT, we hypothesize that RDX elicits seizures by inhibition of neuronal cell repolarization postaction potential leading to heightened neuronal excitability and seizures facilitated by multiple molecular mechanisms. Male Northern Bobwhite 14 Day 2,6-DNT Exposure, Brain Tissue Investigation (High Laser Intensity Scan): Juvenile male and female Northern bobwhite (12 weeks of age) were dosed with 2,6-DNT by daily gavage (0, 50, 100, 190, or 350 mg/kg/day). Each treatment group included seven birds (at least three of each sex per treatment). This microarray data set represents investigation of the male birds. Microarray experiments were conducted using an interwoven-loop design using Cyanine-3 (Cy3) and A647. This experiment investigated the effects of the 14-day 2,6-DNT exposure in males including controls and 60 mg/kg/day treatments, each including 3 biological replicates. To broaden signal detection, each microarray was scanned at high and low laser power to resolve low-intensity spots and reduce signal saturation, respectively (Skibbe et al., 2006). This dataset represents the High Intensity Scan.
2011-11-23 | E-GEOD-33932 | biostudies-arrayexpress