The principal toxicity of acute organophosphate (OP) pesticides poisoning is the disruption of neurotransmission through inhibition of acetylcholinesterase (AChE). However, other mechanisms leading to persistent effects and neurodegeneration remain controversial and difficult to detect. Because Caenorhabditis elegans is relatively resistant to OP lethalityparticularly through the inhibition of AChEstudies in this nematode provide an opportunity to observe alterations in global gene expression following OP exposure that cannot be readily observed in less resistant organisms.
Alterations in gene expression in Caenorhabditis elegans associated with organophosphate pesticide intoxication and recovery.
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View SamplesEffective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression.
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View SamplesMany heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the of toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays.
Exposure to nickel, chromium, or cadmium causes distinct changes in the gene expression patterns of a rat liver derived cell line.
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View SamplesEffective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression.
No associated publication
No sample metadata fields
View SamplesU.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.
Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.
Specimen part, Treatment
View SamplesCobalt is a transition group metal present in trace amounts in the human diet, but in larger doses it can be acutely toxic or cause adverse health effects in chronic, long term exposures. Its use in many industrial processes and alloys worldwide presents opportunities for occupational exposures, as well as exposures to military personnel. While the toxic effects of cobalt have been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify potential biomarkers of exposure or effect, we exposed two rat liver-derived cell lines, H4-II-E-C3 and MH1C1, to two concentrations of cobalt chloride. We examined changes in gene expression using DNA microarrays in both cell lines and examined changes in cytoplasmic protein abundance in MH1C1 cells using mass spectrometry. We chose to closely examine differentially expressed genes and proteins changing in abundance in both cells lines in order to remove cell line specific effects. We identified enriched pathways, networks, and biological functions using commercial bioinformatic tools and manual annotation. Many of the genes, proteins, and pathways modulated by exposure to cobalt appear to be due to an induction of a hypoxic-like response and oxidative stress. Genes that may be differentially expressed due to a hypoxic-like response are involved in Hif-1 signaling, glycolysis, gluconeogenesis, and other energy metabolism related processes. Gene expression changes linked to oxidative stress are also known to be involved in the NRF2-mediated response, protein degradation, and glutathione production. Using microarray and mass spectrometry analysis, we were able to identify modulated genes and proteins, further elucidate the mechanisms of toxicity of cobalt, and identify biomarkers of exposure and effect in vitro, providing targets for focused in vitro studies.
Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
Cell line
View SamplesHuman and mouse blood each contain two monocyte subsets. Here, we investigated the extent of their similarity using a microarray approach. Approximately 300 genes in human and 550 genes in mouse were differentially expressed between subsets. More than 130 of these gene expression differences were conserved between mouse and human monocyte subsets. We confirmed numerous differences at the cell surface protein level. Despite overall conservation, some molecules were conversely expressed between the two species subsets, including CD36, CD9, and TREM-1. Furthermore, other differences existed, including a prominent PPAR signature in mouse monocytes absent in human. Overall, human and mouse monocyte subsets are far more broadly conserved than currently recognized. Thus, studies in mice may indeed yield relevant information regarding the biology of human monocyte subsets. However, differences between the species deserve consideration in models of human disease studied in the mouse.
Comparison of gene expression profiles between human and mouse monocyte subsets.
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View SamplesTransforming growth factor (TGF)-1 is a multifunctional cytokine regulating a number of physiological and patho-physiological processes in the adult brain. Its expression is elevated during neurodegeneration, which is associated with reduced levels of neurogenesis. We have postulated that TGF-1 might be one of the crucial factors involved in limiting neurogenesis in the diseased brain.
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Age
View SamplesTransforming growth factor (TGF)-1 is a multifunctional cytokine regulating a number of physiological and patho-physiological processes in the adult brain. Its expression is elevated during neurodegeneration, which is associated with reduced levels of neurogenesis. We have postulated that TGF-1 might be one of the crucial factors involved in limiting neurogenesis in the diseased brain.
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Age, Specimen part
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
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