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GSE14555
Homo sapiens, Rattus norvegicus
61 Downloadable Samples
Affymetrix Rat Genome U34 Array (rgu34a), Affymetrix Human Genome U133A Array (hgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Divergent transcriptomic responses to aryl hydrocarbon receptor agonists between rat and human primary hepatocytes.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a), Affymetrix Human Genome U133A Array (hgu133a)
Description
(Abstract) Toxicogenomics has great potential for enhancing our understanding of environmental chemical toxicity, hopefully leading to better-informed human health risk assessments. This study employed toxicogenomic technology to reveal species differences in response to two prototypical aryl hydrocarbon receptor (AHR) agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the polychlorinated biphenyl (PCB) congener PCB 126. Dose responses of primary cultures of rat and human hepatocytes were determined using species-specific microarrays sharing over 4,000 gene orthologs. Forty-seven human and 79 rat genes satisfied dose response criteria for both chemicals and were subjected to further analysis including the calculation of EC50 and the relative potency (REP) of PCB 126 for each gene. Only 5 responsive orthologous genes were shared between the two species, yet the geometric mean of the REPs for all rat and human modeled responsive genes were 0.06 (95% Confidence Interval (CI); 0.03-0.1) and 0.002 (95% CI; 0.001-0.005), respectively, suggesting broad species differences in the initial events that follow AHR activation but precede toxicity. This indicates that there are species differences in both the specific genes that responded and the agonist potency and relative potency for those genes. This observed insensitivity of human cells to PCB 126 is consistent with more traditional measurements of AHR activation (i.e., CYP1A1 enzyme activity) and suggests that the species difference in PCB 126 sensitivity is likely due to certain aspects of AHR function. That a species divergence also exists in this expanded AHR-regulated gene repertoire is a novel finding and should help when extrapolating animal data to humans.
Publication Title
Divergent transcriptomic responses to aryl hydrocarbon receptor agonists between rat and human primary hepatocytes.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Rattus norvegicus
- 26 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
(Abstract) Toxicogenomics has great potential for enhancing our understanding of environmental chemical toxicity, hopefully leading to better-informed human health risk assessments. This study employed toxicogenomic technology to reveal species differences in response to two prototypical aryl hydrocarbon receptor (AHR) agonists, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the polychlorinated biphenyl (PCB) congener PCB 126. Dose responses of primary cultures of rat and human hepatocytes were determined using species-specific microarrays sharing over 4,000 gene orthologs. Forty-seven human and 79 rat genes satisfied dose response criteria for both chemicals and were subjected to further analysis including the calculation of EC50 and the relative potency (REP) of PCB 126 for each gene. Only 5 responsive orthologous genes were shared between the two species, yet the geometric mean of the REPs for all rat and human modeled responsive genes were 0.06 (95% Confidence Interval (CI); 0.03-0.1) and 0.002 (95% CI; 0.001-0.005), respectively, suggesting broad species differences in the initial events that follow AHR activation but precede toxicity. This indicates that there are species differences in both the specific genes that responded and the agonist potency and relative potency for those genes. This observed insensitivity of human cells to PCB 126 is consistent with more traditional measurements of AHR activation (i.e., CYP1A1 enzyme activity) and suggests that the species difference in PCB 126 sensitivity is likely due to certain aspects of AHR function. That a species divergence also exists in this expanded AHR-regulated gene repertoire is a novel finding and should help when extrapolating animal data to humans.
Publication Title
No associated publication
Alternate Accession IDs
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
Chronic exposure of Sprague-Dawley (SD) rats to either 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or Aroclor 1254 results in female-selective induction of hepatic tumors. The relative potency of dioxins and PCB mixtures, such as Aroclor 1254, is often estimated using the internationally endorsed toxic equivalency (TEQ) approach. Comparing the genome wide changes in gene expression in both genders following exposure to toxic equivalent doses of these chemicals should identify critical sets of early response genes while further defining the concept of the TEQ of halogenated aromatic hydrocarbons. Aroclor 1254 at 0.6, 6.0 and 60 mg/kg body weight and TEQ doses of TCDD (0.3 and 3.0 g/kg), calculated to match the top two Aroclor 1254 doses, were orally administered to SD rats for three consecutive days. Day 4 gene expression in hepatic tissue was determined using microarrays. A linear mixed-effects statistical model was developed to analyze the data in relation to treatment, gender, and gender*treatment (G*T) interactions. The genes most changed included 54 genes with and 51 genes without a significant model G*T term. The known aryl hydrocarbon receptor (AHR) battery genes (Cyp1a1, Cyp1a2, Cyp1b1, Aldh3a1), and novel genes, responded in a TEQ dose-dependent manner in both genders. However, an important observation was the apparent disruption of sexually dimorphic basal gene expression, particularly for female rats. Since many of these genes are involved in steroid metabolism, exposure to either TCDD or Aroclor 1254 could disrupt proliferative signals more in female rats as a possible consequence of altered estrogen metabolism. This study extends the findings of previous rodent bioassays by identifying groups of genes, other than the well-characterized AHR response genes, whose disruption may be important in the tumorigenic mechanism in this rat strain.
Publication Title
Toxicogenomic analysis of gender, chemical, and dose effects in livers of TCDD- or aroclor 1254-exposed rats using a multifactor linear model.
Alternate Accession IDs
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 856 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global
Publication Title
A genomic storm in critically injured humans.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 587 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Blood was sampled from severe burns patients over time as well as healthy subjects. Genome-wide expression analyses were conducted using the Affymetrix U133 plus 2.0 GeneChip.
Publication Title
Genomic responses in mouse models poorly mimic human inflammatory diseases.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 182 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma.
Publication Title
A genomic score prognostic of outcome in trauma patients.
Alternate Accession IDs
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 144 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We report here the genes that are sequentially expressed in white blood cells from blood and spleen at 2 hours, 2 day,3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Includes WBC treated with LPS for 2 hours and 1 day.
Publication Title
Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus, Homo sapiens
- 85 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
STAT6 transcription factor is a facilitator of the nuclear receptor PPARγ-regulated gene expression in macrophages and dendritic cells.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Treatment, Subject, Time
View Samples