Effect of 52 weeks of chronic exposure to TCDD AND PCB126 on hepatic gene expression
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: James Olson
PROVIDER: E-GEOD-22263 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD and PCB126 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg/day) (Toxic equivalence factor (TEF) = 1.0), PCB126 (30ng, 300ng or 1000ng/kg/day) (TEF = 0.1) or a vehicle control of corn oil:acetone (99:1) 5 days a week for 52 weeks.
2010-06-10 | GSE22263 | GEO
Project description:This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD, PCB126 and PeCDF; the non-AhR ligand PCB153 and the binary mixture PCB126/PCB153 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg), PeCDF (200ng/kg), PCB126 (1000ng/kg) and PCB153 (1000ug/kg) 5 days a week for 13 weeks. Experiment Overall Design: There are 6 control chips and representing animals treated with vehicle control. There are 3 biological replicates (3 chips) for each treatment group (eg. TCDD, PCB126), each biological replicate is derived from 2 individual animals. A total of 21 chips were analyzed. Intensities were normalized using the GC-Robust Multiarray (GCRMA) method through Genetraffic software package.
2008-06-14 | E-GEOD-5789 | biostudies-arrayexpress
Project description:This study investigates the effects of the aryl hydrocarbon receptor (AhR) ligands TCDD, PCB126 and PeCDF; the non-AhR ligand PCB153 and the binary mixture PCB126/PCB153 on hepatic gene expression in female sprague dawley rats. Rats were treated with toxicological equivalent doses of TCDD (100ng/kg), PeCDF (200ng/kg), PCB126 (1000ng/kg) and PCB153 (1000ug/kg) 5 days a week for 13 weeks. Keywords: Environmental pollutant toxicity comparison
2006-09-08 | GSE5789 | GEO
Project description:The dioxin congener 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a wide range of toxic effects in rodent species, all of which are mediated by a ligand-dependent transcription-factor, the aryl hydrocarbon receptor (AHR). The Han/Wistar (Kuopio) (H/W) strain shows exceptional resistance to many TCDD-induced toxicities; the LD50 of >9600 µg/kg for H/W rats is higher than for any other wild-type mammal known. We have previously shown that this resistance primarily results from H/W rats expressing a variant AHR isoform that has a substantial portion of the AHR transactivation domain deleted. Despite this large deletion, H/W rats are not entirely refractory to the effects of TCDD; the variant AHR in these animals remains fully competent to up-regulate well-known dioxin-inducible genes. TCDD-sensitive (Long-Evans, L-E) and resistant (H/W) rats were treated with either corn-oil (with or without feed-restriction) or 100 µg/kg TCDD for either four or ten days. Hepatic transcriptional profiling was done using microarrays, and was validated by RT-PCR analysis of 41 genes. . A core set of genes was altered in both strains at all time points tested, including CYP1A1, CYP1A2, CYP1B1, Nqo1, Aldh3a1, Tiparp, Exoc3, and Inmt. Outside this core, the strains differed significantly in the breadth of response: three-fold more genes were altered in L-E than H/W rats. At ten days almost all expressed genes were dysregulated in L-E rats, likely reflecting emerging toxic responses. Far fewer genes were affected by feed-restriction, suggesting that only a minority of the TCDD-induced changes are secondary to the wasting syndrome. Rats from sensitive (Long-Evans, LE) and resistant (Han/Wistar, HW) strains were treated with 100 ug/kg TCDD or corn oil vehicle and sacrificed either 4 or 10 days after treatment. LE control rats were either fed normally or feed-restricted to control for the wasting effects of TCDD treatment. Each treatment group contains four or five animals (biological replicates), each of which was assayed on an individual microarray.
2011-11-14 | E-GEOD-13513 | biostudies-arrayexpress
Project description:We profiled hepatic transcriptional responses of 6 strains of rats with varying sensitivity to a dioxin, TCDD, at 19 hours following exposure. The resistant rats exhibited significantly reduced transcriptional responses in comparison to the sensitive strains. We hypothesize that genes which show differential changes between the resistant and sensitive rats may potentially explain sensitivity. Rats with varying sensitivities (Long-Evans, L-E; Han/Wistar, H/W; Fischer 344, F344; Wistar, Wis; Line-A, Ln-A; and Line-C, Ln-C) were treated with 100 ug/kg TCDD or corn oil vehicle and euthanized 19 hours post-treatment. Each treatment group contains four or six animals (biological replicates), each of which was assayed on an individual microarray.
2011-08-16 | E-GEOD-31411 | biostudies-arrayexpress
Project description:In many mammals, halogenated aromatic hydrocarbon (HAH) exposure causes wasting syndrome, defined as lethal weight loss as a result of severe and persistent hypophagia. The most potent HAH in causing wasting is 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), which exerts its toxic effects through the aryl hydrocarbon receptor (AHR) – a transcription factor. Because TCDD toxicity is thought to predominantly arise from dysregulation of AHR-transcribed genes, we hypothesized that wasting syndrome is due to TCDD-induced dysregulation of genes involved in regulation of food-intake. We therefore focused on the hypothalamus, as it is the regulatory center of food-intake and energy balance in the central nervous system. We profiled mRNA abundance in hypothalamic tissue from two rat strains with widely differing sensitivities to wasting syndrome: TCDD-sensitive Long-Evans rats and TCDD-resistant Han/Wistar rats, 23 hours after exposure to TCDD (100 μg/kg) or corn oil vehicle. We found that TCDD exposure caused minimal transcriptional dysregulation effects in the hypothalamus, with only 6 genes changed in Long-Evans rats and 15 genes in Han/Wistar rats. Two of the most dysregulated genes were Cyp1a1 and Nqo1, which are induced by TCDD across a wide range of tissues and are considered sensitive markers of TCDD exposure. The minimal response of the hypothalamic transcriptome to a lethal dose of TCDD at an early time-point suggests that the hypothalamus is not the predominant site of initial events leading to hypophagia and associated wasting. TCDD may affect feeding behaviour via events upstream or downstream of the hypothalamus, and further work is required to evaluate this at the level of individual hypothalamic nuclei and subregions. Two strains, each with drug-treated vs vehicle-control
2014-12-23 | E-GEOD-61039 | biostudies-arrayexpress
Project description:Male Sprague Dawley rats were treated orally for 5 days with reference hepatotoxicants, each at a single dose level, alpha-naphthylisothiocyanate 100mg/kg (vehicle 5ml/kg corn oil); carbon tetrachloride 1582mg/kg (vehicle 5ml/kg corn oil); methylenedianiline 100mg/kg (vehicle 35% ethanol); acetaminophen 1000mg/kg (vehicle 2ml/kg corn oil); diclofenac 10mg/kg (vehicle 10ml/kg water)
2018-11-20 | GSE122315 | GEO
Project description:Male Sprague Dawley rats were treated orally for 5 days with reference hepatotoxicants, each at a single dose level alpha-naphthylisothiocyanate 100mg/kg (vehicle 5ml/kg corn oil); carbon tetrachloride 1582mg/kg (vehicle 5ml/kg corn oil); methylenedianiline 100mg/kg (vehicle 35% ethanol); acetaminophen 1000mg/kg (vehicle 2ml/kg corn oil); diclofenac 10mg/kg (vehicle 10ml/kg water)
2018-11-06 | GSE122184 | GEO
Project description:In many mammals, halogenated aromatic hydrocarbon (HAH) exposure causes wasting syndrome, defined as lethal weight loss as a result of severe and persistent hypophagia. The most potent HAH in causing wasting is 2,3,7,8-tetrachlorodibenzo-ρ-dioxin (TCDD), which exerts its toxic effects through the aryl hydrocarbon receptor (AHR) – a transcription factor. Because TCDD toxicity is thought to predominantly arise from dysregulation of AHR-transcribed genes, we hypothesized that wasting syndrome is due to TCDD-induced dysregulation of genes involved in regulation of food-intake. We therefore focused on the hypothalamus, as it is the regulatory center of food-intake and energy balance in the central nervous system. We profiled mRNA abundance in hypothalamic tissue from two rat strains with widely differing sensitivities to wasting syndrome: TCDD-sensitive Long-Evans rats and TCDD-resistant Han/Wistar rats, 23 hours after exposure to TCDD (100 μg/kg) or corn oil vehicle. We found that TCDD exposure caused minimal transcriptional dysregulation effects in the hypothalamus, with only 6 genes changed in Long-Evans rats and 15 genes in Han/Wistar rats. Two of the most dysregulated genes were Cyp1a1 and Nqo1, which are induced by TCDD across a wide range of tissues and are considered sensitive markers of TCDD exposure. The minimal response of the hypothalamic transcriptome to a lethal dose of TCDD at an early time-point suggests that the hypothalamus is not the predominant site of initial events leading to hypophagia and associated wasting. TCDD may affect feeding behaviour via events upstream or downstream of the hypothalamus, and further work is required to evaluate this at the level of individual hypothalamic nuclei and subregions.
2014-12-23 | GSE61039 | GEO
Project description:Major toxicities of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) result from dysregulation of gene expression mediated by the aryl hydrocarbon receptor (AHR). Dioxin-like chemicals alter expression of numerous genes in liver but the specific genes whose dysregulation leads to toxicities such as wasting, hepatotoxicity and lethality have not been identified. We searched for genes that are most likely to be key to dioxin toxicity by using gene expression arrays to contrast hepatic gene expression after TCDD treatment in dioxin-sensitive rats (that carry wildtype AHR) with gene expression in H/W(Kuopio) rats which are highly resistant to dioxin toxicity due to a major deletion in the AHR's transactivation domain (TAD). The total number of TCDD-responsive genes was smaller in rats with the AHRH/W genotype than in rats with wildtype AHR. However, genes in the classic AH gene battery such as CYP1A1, CYP1A2 and CYP1B1 remained fully responsive to TCDD in AHRH/W rats; thus the TAD deletion selectively interferes with expression of a subset of hepatic genes rather than abolishing global AHR-mediated responses. Genes in the following functional categories differ in response to TCDD between dioxin-sensitive rats and dioxin-resistant rats: fatty acid oxidation, metabolism (xenobiotic, alcohol, amino acid, and fatty acid), phosphate transport, regulation of steroid biosynthesis, nitrogen compound catabolism, and generation of precursor metabolites and energy. Many of these differentially-responsive genes are integral parts of pathways such as: protein degradation and synthesis, fatty acid metabolism and synthesis, cytokinesis, cell growth, and apoptosis which may be part of mechanisms which lead to TCDD-induced wasting, hepatotoxicity, tumors, and death. These differentially-responsive genes are worthy candidates for further mechanistic studies to test their role in mediating or protecting from major dioxin toxicities. Experiment Overall Design: Four strains of rats were either treated with 100 ug/kg TCDD or cornoil vehicle and profiled at 19 hours, each with four replicates. Two strains were also analyzed at 3 hours, each with four replicates.
2009-12-02 | E-GEOD-10083 | biostudies-arrayexpress