Exposure of an immortalized human bronchial epithelial cell line, BEAS-2B, to one of four metals (arsenic, chromium, nickel or vanadium) to determine the early changes that lead to cell transformation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE36684 | GEO | 2012/03/22
SECONDARY ACCESSION(S): PRJNA153597
REPOSITORIES: GEO
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Project description:To determine early changes leading to human cell transformation (cancer) we exposed an immortalized human bronchial epithelial cell line, BEAS-2B, to one of four different metals that may cause cancer via inhalation in humans or rodents: 2.0 micro-Molar soluble sodium arsenite (NaAsO2), 0.50 micro-Molar potassium chromate (K2CrO4), 250 micro-Molar nickel (II) sulfate (NiSO4), 10 micro-Molar sodium meta-vanadate (NaVO3), or were left untreated (control). After a 30-60 day exposure, cells were rinsed of metals and seeded in soft agar. A small number of the cells formed colonies in the soft agar, demonstrating the potential for anchorage independent growth, a characteristic of cancer. These colonies that originated from a single cell were extracted from the agar and grown out in monolayer for 3-4 weeks. The RNA data provided here is taken from these cells. The significance it that the metal exposure was stopped many generations before the analysis, yet each sample demonstrates changes in gene expression based on the original metal exposure. A total of 39 samples were analyzed, consisting of 3 parental cell lines (BEAS-2B cells that were never seeded in agar or exposed to any metal), 11 controls cells (grouped into three sets, based on those seeded at the same time as the V-treated clones, the Cr-treated clones, or the As-treated and Ni-treated clones), and 25 metal-treated clones (7 each for Ni and As, processed in two separate batches of 3 and 4 clones each, 6 Cr clones and 5 Vanadium clones). Because the samples were processed in different batches, the data was batch-normalized using the COMBAT package in R prior to importing into GeneSpring. Once in GeneSpring the data was base-lined with each sample compared to its control samples (Batch 1: Cr 1-6, P-2, Ctrls 6-8; Batch 2: As1-3, Ni 1-3, P-1 and Ctrl 1-3; Batch 3: As4-7, Ni 4-7, and Ctrl 4-5; Batch 4: V 1-5, P-3 and Ctrl 9-11). When the same analysis was performed but with baseline of samples to all controls combined, a similar result was obtained, albeit with less tight clustering. Arsenic clones 2 and 5 appear to be outliers as their removal nicely cleans up the PCA, but this appears to be genuine biological variation as we did not identify any significant problems with the data.
2012-03-22 | E-GEOD-36684 | biostudies-arrayexpress
Project description:RNAseq transcriptomic analysis of MCF10A-CT, MC26 and M1B26 cell lines. MCF10A cells are human not transformed mammary stem-like cells that do not form colonies in soft-agar assay and do not engraft in immunocompromised mice. MC26 are MCF10A derivatives that were submitted to long-term culture in presence of human recombinant BMP2 and IL6 for several weeks until colony formation in soft-agar was detected. M1B26 are MCF10A derivatives that were sorted for high expression of the BMPR1b BMP receptor prior to BMP2 and IL6 treatment and expanded from several soft-agar colonies. M1B26 are more transformed than MC26 based on the frequency of soft-agar colonies forming cells and on the ability to engraft in mice. As a control, MCF10A-CT were kept in culture for similar length of time than MC26 and M1B26 but without BMP2 and IL6 and do not generate soft-agar colonies or engraft in mice. This study aims to document the transcriptomic changes associated with early transformation events mediated by abnormal exposure to BMP2 and inflammatory signal.
2023-09-01 | GSE186734 | GEO
Project description:Many veterans live with military grade heavy metal fragments retained in soft tissue. Retained heavy metal fragments may negatively impact health in various organ systems and can manifest as gastrointestinal, neurocognitive, pulmonary and renal disturbances. As such, a better understanding of the long-term effects of retained metals and identification of biomarkers indicative of detrimental health outcomes would benefit clinical decision making. In this study, we analyzed urine microRNAs from rats with military-relevant pure metals implanted in the gastrocnemius muscle for 1, 3, 6, and 12 months. Our results provide potential tissue targets affected by metal exposure and a list of unique or common urine microRNA biomarkers indicative of exposure to one or more metals, highlighting a complex systemic response.
2021-09-28 | GSE167948 | GEO
Project description:Many veterans live with military grade heavy metal fragments retained in soft tissue. Retained heavy metal fragments may negatively impact health in various organ systems and can manifest as gastrointestinal, neurocognitive, pulmonary and renal disturbances. As such, a better understanding of the long-term effects of retained metals and identification of biomarkers indicative of detrimental health outcomes would benefit clinical decision making. In this study, we analyzed serum microRNAs from rats with military-relevant pure metals implanted in the gastrocnemius muscle for 1, 3, 6, and 12 months in order to identify potential microRNA biomarkers that are indicative of exposure to one or more metals.
2023-05-01 | GSE168757 | GEO
Project description:Using transcriptomics, we studied the spatiotemporal dynamics of B. subtilis swarming colonies on soft-agar surface and identified functional subpopulations.
2023-09-20 | GSE224332 | GEO
Project description:Pentavalent vanadium compounds induce intracellular changes in vitro that are consistent with those of other carcinogenic substances, including alteration of transcription factor levels, promotion of oxidative stress, inflammation, DNA damage, stimulation of mitogenic signals, and suppression of apoptosis. While there is no clear evidence that vanadium compounds cause cancer in humans, vanadium pentoxide causes lung cancer in rodents after long-term inhalation exposures and in turn IARC has categorized it as a group 2B possible human carcinogen. The goal of this study was to investigate the carcinogenicity of NaVO3 in the human immortalized bronchial epithelial cell line, Beas-2B. Cells were treated with 10 µM NaVO3 for 5 weeks, with or without recovery time, followed by gene expression microarray analysis. In a separate experiment, cells were exposed to 1-10 µM NaVO3 for 4 weeks and then grown in soft agar to test for anchorage-independent growth. A dose-dependent increase in the number of colonies was observed. NaVO3-transformed clones could repair a wound faster than controls during the scratch test. In a gene expression microarray analysis of soft agar clones there were 2010 differentially expressed genes (DEG) (adjusted p-value ⤠0.05) in NaVO3-transformed clones relative to control clones. DEG from this experiment were compared with the DEG of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values <0.05, and 469 genes were altered in the same direction for transformed clones, 5 week NaVO3-treated cells, and the recovered cells; a subset of these changes were validated by QRT-PCR. The data from this study imply that chronic exposure to NaVO3 causes changes that are consistent with cellular transformation including anchorage- independent growth, enhanced migration ability, and gene expression changes that were epigenetically inherited through cell division. Beas-2B cells were chronically exposed to sodium metavanadate in growth media for 4 weeks. Then exposed cells and unexposed control cells were grown in soft agar for 3 weeks in the absence of vanadate. Transformed colonies (arising from vanadate-exposed cells) and control colonies (spontaneously grew from unexposed cells) were extracted from soft agar and expanded in the absence of vanadate, then processed for gene expression analysis on Affymetrix GeneChip Human Exon 1.0 ST array. 5 transformed clones, 3 control clones, 1 parental Beas-2B cell sample, and acute 24 hour vanadate exposed cell samples were analyzed.
2013-01-19 | E-GEOD-43386 | biostudies-arrayexpress
Project description:Pentavalent vanadium compounds induce intracellular changes in vitro that are consistent with those of other carcinogenic substances, including alteration of transcription factor levels, promotion of oxidative stress, inflammation, DNA damage, stimulation of mitogenic signals, and suppression of apoptosis. While there is no clear evidence that vanadium compounds cause cancer in humans, vanadium pentoxide causes lung cancer in rodents after long-term inhalation exposures and in turn IARC has categorized it as a group 2B possible human carcinogen. The goal of this study was to investigate the carcinogenicity of NaVO3 in the human immortalized bronchial epithelial cell line, Beas-2B. Cells were treated with 10 M-BM-5M NaVO3 for 5 weeks, with or without recovery time, followed by gene expression microarray analysis. In a separate experiment, cells were exposed to 1-10 M-BM-5M NaVO3 for 4 weeks and then grown in soft agar to test for anchorage-independent growth. A dose-dependent increase in the number of colonies was observed. NaVO3-transformed clones could repair a wound faster than controls during the scratch test. In a gene expression microarray analysis of soft agar clones there were 2010 differentially expressed genes (DEG) (adjusted p-value M-bM-^IM-$ 0.05) in NaVO3-transformed clones relative to control clones. DEG from this experiment were compared with the DEG of 5 week NaVO3 exposure with or without recovery, all with adjusted p-values <0.05, and 469 genes were altered in the same direction for transformed clones, 5 week NaVO3-treated cells, and the recovered cells; a subset of these changes were validated by QRT-PCR. The data from this study imply that chronic exposure to NaVO3 causes changes that are consistent with cellular transformation including anchorage- independent growth, enhanced migration ability, and gene expression changes that were epigenetically inherited through cell division. Beas-2B cells were chronically exposed to sodium metavanadate in growth media for 4 weeks. Then, one set of exposed cells and unexposed control cells were grown in soft agar for 3 weeks in the absence of vanadate. Transformed colonies (arising from vanadate-exposed cells) and control colonies (spontaneously grew from unexposed cells) were extracted from soft agar and expanded in the absence of vanadate, then processed for gene expression analysis . A second set of exposed cells continued treatment for a total of 5 weeks exposure. A third set of cells recovered for 1 week after the 4 week long exposure. The gene expression of 5 transformed clones, 3 control clones, 2 5 week exposures, 2 recovery, and 2 unexposed control cells, and 1 parental Beas-2B cell samples were analyzed (15 total samples) with an Affymetrix GeneChip Human Exon 1.0 ST array.
2013-01-19 | E-GEOD-43593 | biostudies-arrayexpress
Project description:This study was designed to follow the transcriptome changes during BMP2 mediated transformation of the MCF10A human mammary stem cell model. We found that long-term BMP2/IL6 exposure of MCF10A cells, human immortalized but non-transformed mammary stem cells and progenitors, led to their luminal transformation. MC26 cells correspond to MCF10A cells transformed by BMP2/IL6 long-term exposure and contrarily to their parental cells, are able to engraft in immunodeficient mice and form colonies in soft-agar. M1B26 cells were obtained after BMP2/IL-6 long-term treatment of MCF10A cells sorted for high BMPR1B expression and subsequent isolation and expansion of 3 soft-agar colonies. M1B26 have an increased ability to engraft in mice and form colonies in soft-agar when compared to MC26 cells. As a non-transformed control, MCF10A-CT cells were kept in culture without BMP2/IL6 for the same length of time than MC26 cells. MCF10A-CT, MC26 and M1B26 cells are thus a model allowing to follow the molecular events associated with the initiation of a luminal transformation in mammary stem cells. Expression of the CD10 membrane endopeptidase has been associated with cancer although it can be a marker of both good or poor prognosis depending on the stage of the cancer and on the tissue of origin. In addition, we showed that CD10 was a marker of stem cell containing populations in healthy mammary tissue and that CD10 enzymatic activity was involved in the maintenance of cells immature properties. Having recently shown that CD10 expression was increasing during BMP2 mediated transformation and that CD10 expressing cells were more transformed but that CD10 was not required for transformation, we set out to determine the gene signature associated with CD10 expression.
2023-09-01 | GSE123053 | GEO
Project description:Metal toxicity is a global environmental challenge. Fish are particularly prone to metal exposure, which can be lethal or can cause sublethal physiological impairments. The objective of this study was to improve our understanding on how adverse effects of essential and non-essential metals in early life stage zebrafish may be explained by changes in the transcriptome after exposure to non-toxic levels. We therefore studied the effects of three different metals at low concentrations in zebrafish embryos by transcriptomics analysis. The study design compared exposure effects caused by different metals at different developmental stages (pre-hatch and post-hatch). Wild-type embryos were exposed to solutions of low concentrations of copper (CuSO4), cadmium (CdCl2) and cobalt (CoSO4) until 96 h post-fertilization (hpf) and microarray experiments were carried out to determine transcriptome profiles at 48 and 96 hpf. We found that the toxic metal cadmium affected the expression of more genes at 96 hpf than 48 hpf. The opposite effect was observed for the essential metals cobalt and copper, which also showed enrichment of different GO terms. Genes involved in neuromast and motor neuron development, were significantly enriched, agreeing with our previous results showing motor neuron and neuromast damage in the embryos. Our data provide evidence that the response of the transcriptome of fish embryos to metal exposure differs for essential and non-essential metals.
2017-12-27 | GSE80957 | GEO
Project description:Background: Prolonged exposure to toxic heavy metals leads to deleterious health outcomes such as kidney injury and irreversible progression to chronic kidney disease. For example, veterans return from the battlefield with increasing amounts of retained metal fragments. Certain community water sources in the US are contaminated with varying levels of heavy metals, including uranium and lead. One of the key challenges is to detect damage to kidney tissue before glomerular filtration rate is affected. Methods: High-throughput transcriptomics (HTT) has recently been demonstrated have high sensitivity and specificity as a rapid and cost-effective assay for detecting tissue toxicity. To better understand the molecular signature of early kidney damage, we performed RNA-seq analysis on renal tissue using a rat model of soft tissue-embedded metal exposure. We them performed small RNA-seq analysis on serum samples from the same animals in an effort to identify miRNA biomarkers of kidney damage. Results: We found that metals, especially lead and depleted uranium, induces oxidative damage that mainly cause dysregulated mitochondrial gene expression. Utilizing publicly available single-cell RNA-seq datasets, we demonstrate that deep learning-based cell type decomposition effectively identified cells within the kidney that were affected by metal exposure. By combining random forest feature selection and statistical methods, we further identify miRNA-423 as a promising early systemic marker of kidney injury. Conclusion: Our data suggests that combining HTT and deep learning represents a promising approach for identifying cell injury in kidney tissue. We propose miRNA-423 as a potential serum biomarker for early detection of kidney injury.
2022-12-01 | GSE203624 | GEO