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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

ABSTRACT: 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.

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.

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 ÂµM 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 ÂµM 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 â¤ 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.

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.

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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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