The present study aims to examine the toxicological effects of phenanthrene in the molecular mechanism in zebrafish. We performed RNA-Seq analysis on zebrafish liver responding to phenanthrene exposure. Genes involved in phenanthrene exposure to zebrafish liver were identified from the transcriptional data. This study provides the completed evaluation of toxic effect of phenanthrene exposure to zebrafish by transcriptional approaches. Our findings could present foundation for further study on molecular mechanism responsible for zebrafish's responses to phenanthrene exposure.
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View SamplesHumans and ecological species have been found to have detectable body burdens of a number of perfluorinated alkyl acids (PFAA) including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). In mouse and rat liver these compounds elicit transcriptional and phenotypic effects similar to peroxisome proliferator chemicals (PPC) that work through the nuclear receptor peroxisome proliferator activated receptor alpha (PPARalpha). Recent studies indicate that along with PPARalpha other nuclear receptors are required for transcriptional changes in the mouse liver after PFOA exposure including the constitutive activated receptor (CAR) and pregnane X receptor (PXR) that regulate xenobiotic metabolizing enzymes (XME). To determine the potential role of CAR/PXR in mediating effects of PFAAs in rat liver, we performed a meta-analysis of transcript profiles from published studies in which rats were exposed to PFOA or PFOS. We compared the profiles to those produced by exposure to prototypical activators of CAR (Phenobarbital (PB)), PXR (pregnenolone 16 alpha-carbonitrile (PCN)), or PPARalpha (WY-14,643 (WY)). As expected, PFOA and PFOS elicited transcript profile signatures that included many known PPARalpha target genes. Numerous XME genes were also altered by PFOA and PFOS but not WY. These genes exhibited expression changes shared with PB or PCN. Reexamination of the transcript profiles from the livers of chicken or fish exposed to PFAAs indicated that PPARalpha, CAR, and PXR orthologs were not activated. Our results indicate that PFAAs under these experimental conditions activate PPARalpha, CAR, and PXR in rats but not chicken and fish. Lastly, we discuss evidence that human populations with greater CAR expression have lower body burdens of PFAAs.
Evidence for the involvement of xenobiotic-responsive nuclear receptors in transcriptional effects upon perfluoroalkyl acid exposure in diverse species.
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View SamplesHuman Hepatocellular Carcinoma cells (HepG2) were exposed to six nanomaterials containing either Cerium oxide (CeO2) or Titanium oxide (TiO2) nanoparticles. Three different concentrations were tested: 0.3, 3, or 30 g/mL) for 3 days. Microarray analysis was performed to identify genes differentially expressed following exposure to these chemicals.
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Specimen part, Cell line
View SamplesIn order to gain insight into the effects of aging on susceptibility to environmental toxins, we characterized the expression of xenobiotic metabolizing enzymes (XMEs) from the livers of male Brown Norway and F344 rats across the adult lifespan. To examine metabolic processes across lifespan after challenge with a xenobiotic compound, Brown Norway rats were exposed to 1.0 g/kg body weight toluene by oral gavage in corn oil (4ml/kg body weight) or corn oil alone.
Coordinated changes in xenobiotic metabolizing enzyme gene expression in aging male rats.
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View SamplesUsing full-genome arrays, the expression of all XMEs was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND30), middle age (12 mon), and old age (18 and 24 mon) in the C57Bl6/J mouse liver and compared to young adults. Fetal and neonatal life stages had a dramatic effect on XME expression compared to the relatively minor effects of old age. At all life stages except PND30 down-regulated genes outnumbered up-regulated genes. The altered XMEs included those in all of the major metabolic phases including phase I (alcohol and aldehyde dehydrogenase and Cyp genes), phase II (aldo-keto reductase, glutathione-S-transferases, sulfotransferases and UDP-glucuronosyl transferases) and phase III (transporters). We have generated a comprehensive catalog of XME hepatic gene changes through the life stages of the mouse that can be used to predict chemicals and chemical classes different life stages are more sensitive to. Some CEL files used in this study have been submitted through GSE21224.
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Sex, Age, Specimen part
View SamplesWe demonstrate that expression of key markers of keratinocyte differentiation is suppressed by exposure to sodium arsenite. Folate deficiency exacerbates this effect. In addition, cancer-related cell movement genes, and growth and proliferation genes are altered. Several redox-sensitive transcription factors are implicated in mediating these gene expression changes due to arsenic treatment and folate deficiency.
Folate deficiency enhances arsenic effects on expression of genes involved in epidermal differentiation in transgenic K6/ODC mouse skin.
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View SamplesWe hypothesize that there is a set of differentially-expressed gene biomarkers that distinguishes the immune response associated with the induction of allergic sensitization from non-allergic immune responsiveness following a single exposure. The goal of this preliminary study was to identify potential biomarkers that differentiate the response to allergens vs non-allergens following an acute exposure in nave individuals.
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Sex, Age, Specimen part
View SamplesWe characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19.5 and in the neonate (postnatal day (PND) 7 and 30) using full-genome microarrays and compared these changes to that in the adult liver. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were suppressed. Comparison of the dataset to a number of previously published datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) suppression of most xenobiotic metabolism genes throughout development, except a number of transporters associated with expression in hematopoietic cells.
Transcriptional ontogeny of the developing liver.
Specimen part
View SamplesToxicogenomic Dissection of the Perfluorooctanoic Acid (PFOA) Transcript Profile in Mouse Liver: Evidence for the Involvement of Nuclear Receptors PPARalpha and CAR
Toxicogenomic dissection of the perfluorooctanoic acid transcript profile in mouse liver: evidence for the involvement of nuclear receptors PPAR alpha and CAR.
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View SamplesCharacterization of Peroxisome Proliferator-Activated Receptor alpha (PPAR(alpha)) - Independent Effects of PPAR(alpha) Activators in the Rodent Liver: Di-(2-ethylhexyl) phthalate Activates the Constitutive Activated Receptor
Characterization of peroxisome proliferator-activated receptor alpha--independent effects of PPARalpha activators in the rodent liver: di-(2-ethylhexyl) phthalate also activates the constitutive-activated receptor.
Sex, Age, Treatment
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