Global transcriptional analysis of Cr(VI)-adapted cells of Klebsiella sp. AqSCr
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ABSTRACT:
ORGANISM(S): Klebsiella sp. AqSCr
PROVIDER: GSE160968 | GEO | 2021/05/20
REPOSITORIES: GEO
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Project description:In order to evaluate the mechanisms underlying hexavalent chromium (Cr(VI)) responses, mice and rats were treated with varying concentrations of Cr(VI) in drinking water, as sodium dichromate dihydrate (SDD). Potential transcriptomic responses were evaluated through microarray analysis.
2016-09-24 | GSE87259 | GEO
Project description:In order to evaluate the mechanisms underlying hexavalent chromium (Cr(VI)) responses, mice and rats were treated with varying concentrations of Cr(VI) in drinking water, as sodium dichromate dihydrate (SDD). Potential transcriptomic responses were evaluated through microarray analysis.
2016-09-24 | GSE87261 | GEO
Project description:Significant occupational and environmental exposures to hexavalent chromium, a metal with broad toxicity potential in humans, have been reported. In order to understand the mechanisms of dermal toxicity induced by hexavalent chromium, global gene expression profiling of human dermal fibroblasts exposed to a toxic concentration of potassium dichromate was performed. Microarray analysis of the gene expression profile in the fibroblasts treated with potassium dichromate identified significant differential expression of approximately 1,200 transcripts compared with the control cells. Hierarchical cluster analysis of the gene expression profile demonstrated a clear separation of the treated cells from the control group of cells. Functional categorization of the differentially expressed genes identified the enrichment of genes involved in several cellular processes, including apoptosis and oxidative stress, in the fibroblasts exposed to hexavalent chromium. Induction of apoptosis and generation of hydroxyl radicals indicative of oxidative stress in the dermal fibroblasts in response to their exposure to hexavalent chromium were independently confirmed by TUNEL assay and electron spin resonance (ESR) analysis, respectively. The potassium dichromate-induced cytotoxicity, differential gene expression, apoptosis, and oxidative stress were significantly blocked by the addition of ferrous sulfate, an agent known for its ability to reduce hexavalent chromium to the insoluble and therefore impermeable trivalent form, to the cell culture medium. Taken together, our data provide insights into the potential mechanisms underlying the dermal toxicity of hexavalent chromium and suggest a definite role for apoptosis and oxidative stress in Cr(VI)-induced cytotoxicity in human dermal fibroblasts. 16 samples were analyzed in this experiment. Exponentially growing human dermal fibroblasts (3x105 cells) were cultured in T25 cell culture flasks. When the cells were approximately 70% confluent, hexavalent potassium dichromate (5µM) was added to the medium with or without 40µM ferrous sulfate. Following 16 hours of culturing at 37oC, total RNA was isolated for gene expression studies. Details of the samples are: Control 4 Samples: Cr(0)-1, Cr(0)-2, Cr(0)-3, Cr(0)-4 Cr 5 µM 4 Samples: Cr(5)-5, Cr(5)-6, Cr(5)-7, Cr(5)-8 FeSO4 40 µM 4 Samples: Fe(40)-9, Fe(40)-10, Fe(40)-11, Fe(40)-12 Cr 5 µM + FeSO4 40 µM 4 Samples: Cr(5)+Fe(40)-13,Cr(5)+Fe(40)-14, Cr(5)+Fe(40)-15, Cr(5)+Fe(40)-16
2011-07-30 | E-GEOD-16349 | biostudies-arrayexpress
Project description:Significant occupational and environmental exposures to hexavalent chromium, a metal with broad toxicity potential in humans, have been reported. In order to understand the mechanisms of dermal toxicity induced by hexavalent chromium, global gene expression profiling of human dermal fibroblasts exposed to a toxic concentration of potassium dichromate was performed. Microarray analysis of the gene expression profile in the fibroblasts treated with potassium dichromate identified significant differential expression of approximately 1,200 transcripts compared with the control cells. Hierarchical cluster analysis of the gene expression profile demonstrated a clear separation of the treated cells from the control group of cells. Functional categorization of the differentially expressed genes identified the enrichment of genes involved in several cellular processes, including apoptosis and oxidative stress, in the fibroblasts exposed to hexavalent chromium. Induction of apoptosis and generation of hydroxyl radicals indicative of oxidative stress in the dermal fibroblasts in response to their exposure to hexavalent chromium were independently confirmed by TUNEL assay and electron spin resonance (ESR) analysis, respectively. The potassium dichromate-induced cytotoxicity, differential gene expression, apoptosis, and oxidative stress were significantly blocked by the addition of ferrous sulfate, an agent known for its ability to reduce hexavalent chromium to the insoluble and therefore impermeable trivalent form, to the cell culture medium. Taken together, our data provide insights into the potential mechanisms underlying the dermal toxicity of hexavalent chromium and suggest a definite role for apoptosis and oxidative stress in Cr(VI)-induced cytotoxicity in human dermal fibroblasts.
2011-07-31 | GSE16349 | GEO
Project description:Hexavalent Chromium, Cr(VI), exposure is known to cause cancer and is a significant human health concern. While the effect of Cr(VI) exposure on exposed individuals is well studied, long-term effects of the same on the progeny of exposed individual are not known. In this study, using Drosophila model system, we show that Cr(VI) exposure of mothers leads to phenotypic variations in the progeny who have never been exposed to Cr(VI). These phenotypic variations arise due to epigenetic instability in the somatic tissues of the progeny rather than novel genetic mutations. Using a Drosophila cancer model system, we also show that maternal Cr(VI) exposure can lead to cancer phenotypes in the progeny and the propensity to cause cancer phenotypes in the progeny is fixed in the population for at least three generations. Thus, we show for the first time that effects of Cr(VI) exposure can last for several generations. This study also lays the foundation to use Drosophila model system to provide novel insights into Cr(VI) and other heavy metal toxicity.
2019-01-01 | GSE111834 | GEO
Project description:Hexavalent chromium compounds are well-established respiratory carcinogens utilized in industrial processes. While inhalation exposure constitutes an occupational risk affecting mostly chromium workers, environmental exposure from drinking water is a widespread gastrointestinal carcinogen, affecting millions of people throughout the world. Cr(VI) is genotoxic, by forming protein-Cr-DNA adducts and silencing tumor suppressor genes, but its mechanism of action at the molecular level is poorly understood. We have used FAIRE to show that Cr(VI) elicits broad changes in chromatin accessibility resulting from disruption of the binding of transcription factors CTCF and AP-1 to their cognate sites in chromatin. Here, we have used two complementary approaches to test the hypothesis that chromium perturbs chromatin organization and dynamics. DANPOS2 analyses of MNase.seq data identified several chromatin alterations induced by Cr(VI) affecting nucleosome architecture, including occupancy changes at specific genome locations; position shifts of 10 nucleotides or more; and fuzziness, or changes in signal amplitude. Using ATAC to analyze changes in chromatin accessibility, we found that Cr(VI) opened differentially accessible chromatin domains in a dose-dependent manner. These domains were enriched for the previously identified binding motifs for CTCF and AP-1, many located in promoters of differentially expressed genes. Cr(VI)-enriched CTCF sites were confirmed by ChIP.seq and, when compared with ENCODE-validated CTCF site datasets from mouse liver, correlated with evolutionarily conserved similar sites occupied in vivo. Our results show that Cr(VI) exposure promotes broad changes in chromatin accessibility and suggest that the subsequent dysregulation of transcription may result from the disruption of CTCF binding and nucleosome spacing, suggesting that transcription regulatory mechanisms are primary Cr(VI) targets.
2018-01-01 | GSE104565 | GEO
Project description:Hexavalent chromium compounds are well-established respiratory carcinogens utilized in industrial processes. While inhalation exposure constitutes an occupational risk affecting mostly chromium workers, environmental exposure from drinking water is a widespread gastrointestinal carcinogen, affecting millions of people throughout the world. Cr(VI) is genotoxic, by forming protein-Cr-DNA adducts and silencing tumor suppressor genes, but its mechanism of action at the molecular level is poorly understood. We have used FAIRE to show that Cr(VI) elicits broad changes in chromatin accessibility resulting from disruption of the binding of transcription factors CTCF and AP-1 to their cognate sites in chromatin. Here, we have used two complementary approaches to test the hypothesis that chromium perturbs chromatin organization and dynamics. DANPOS2 analyses of MNase.seq data identified several chromatin alterations induced by Cr(VI) affecting nucleosome architecture, including occupancy changes at specific genome locations; position shifts of 10 nucleotides or more; and fuzziness, or changes in signal amplitude. Using ATAC to analyze changes in chromatin accessibility, we found that Cr(VI) opened differentially accessible chromatin domains in a dose-dependent manner. These domains were enriched for the previously identified binding motifs for CTCF and AP-1, many located in promoters of differentially expressed genes. Cr(VI)-enriched CTCF sites were confirmed by ChIP.seq and, when compared with ENCODE-validated CTCF site datasets from mouse liver, correlated with evolutionarily conserved similar sites occupied in vivo. Our results show that Cr(VI) exposure promotes broad changes in chromatin accessibility and suggest that the subsequent dysregulation of transcription may result from the disruption of CTCF binding and nucleosome spacing, suggesting that transcription regulatory mechanisms are primary Cr(VI) targets.
2018-01-01 | GSE104564 | GEO
Project description:Hexavalent chromium compounds are well-established respiratory carcinogens utilized in industrial processes. While inhalation exposure constitutes an occupational risk affecting mostly chromium workers, environmental exposure from drinking water is a widespread gastrointestinal carcinogen, affecting millions of people throughout the world. Cr(VI) is genotoxic, by forming protein-Cr-DNA adducts and silencing tumor suppressor genes, but its mechanism of action at the molecular level is poorly understood. We have used FAIRE to show that Cr(VI) elicits broad changes in chromatin accessibility resulting from disruption of the binding of transcription factors CTCF and AP-1 to their cognate sites in chromatin. Here, we have used two complementary approaches to test the hypothesis that chromium perturbs chromatin organization and dynamics. DANPOS2 analyses of MNase.seq data identified several chromatin alterations induced by Cr(VI) affecting nucleosome architecture, including occupancy changes at specific genome locations; position shifts of 10 nucleotides or more; and fuzziness, or changes in signal amplitude. Using ATAC to analyze changes in chromatin accessibility, we found that Cr(VI) opened differentially accessible chromatin domains in a dose-dependent manner. These domains were enriched for the previously identified binding motifs for CTCF and AP-1, many located in promoters of differentially expressed genes. Cr(VI)-enriched CTCF sites were confirmed by ChIP.seq and, when compared with ENCODE-validated CTCF site datasets from mouse liver, correlated with evolutionarily conserved similar sites occupied in vivo. Our results show that Cr(VI) exposure promotes broad changes in chromatin accessibility and suggest that the subsequent dysregulation of transcription may result from the disruption of CTCF binding and nucleosome spacing, suggesting that transcription regulatory mechanisms are primary Cr(VI) targets.
2018-01-01 | GSE104563 | GEO
Project description:Living organisms are exposed on a daily basis to widespread mixtures of toxic compounds. Mixtures pose a major problem in the assessment of health effects because they often generate substance-specific effects that cannot be attributed to a single mechanism. Two compounds often found together in the environment are the heavy metal chromium and the polycyclic aromatic hydrocarbon benzo[a]pyrene (B[a]P). We have examined how long-term exposure to a low concentration of Cr(VI) affects the transcriptional response to B[a]P, a second toxicant with an unrelated mechanism of action. Growth of mouse hepatoma cells for 20 passages in medium with 0.1 or 0.5 uM Cr(VI) increases DNA damage and apoptosis and decreases clonogenic ability. These cells also show transcriptome changes indicative of increased expression of DNA damage response and repair genes. In them, B[a]P activates cancer progression pathways, unlike cells never exposed to Cr(VI), where B[a]P activates mostly xenobiotic metabolism pathways. Cells grown in Cr(VI) for 20 passages and then cultured for an additional 5 passages in the absence of Cr(VI) recover from some but not all the chromium effects. They show B[a]P-dependent transcriptome changes strongly weighted towards xenobiotic metabolism, similar to those in B[a]P-treated cells that had no previous Cr(VI) exposure, but retain a high level of Cr(VI)-induced DNA damage and silence the expression of DNA damage and cancer progression genes. We conclude that the combined effect of these two toxicants appears to be neither synergistic nor cumulative, generating a toxic/adaptive condition that cannot be predicted from the effect of each toxicant alone. Mouse Hepa-1 cells treated with Cr, Bap, Cr+Bap and untreated were profiled using RNAseq in duplicates.
2013-08-07 | E-GEOD-49571 | biostudies-arrayexpress
Project description:Cr(VI) is a common bioavailable toxic metal that can cause oxidative stress, DNA adducts, and perturb normal gene expression. Changes in gene expression are useful biomarkers of toxicant exposure that provide information about the health of an organism, its ability to adapt to its environment, and indicate potential toxicant-specific effects. Therefore, we developed a toxicology array to the estuarine sentinel species Fundulus heteroclitus, or mummichog. Adults males were exposed to Cr(VI) for 7-days at 0, 1.5 (NOEC), or 3 mg/L (LOEC). Livers were excised and RNA isolated. Adults are used in the laboratory experiments so that we can compare laboratory studies to fish caught at chromium-contaminated field sites. Cr(VI) altered the expression of 12 genes in adult liver, including hepatic growth factor activator, heart fatty acid binding protein, and complement component C3-2. Keywords: dose response
2006-03-31 | GSE3480 | GEO