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Microarray analysis of gene expression in human bronchial epithelial cells exposed to arsenic, BaP alone or arsenic plus BaP

ABSTRACT: Human bronchial epithelial cell BEAS-2B cells were continuously exposed to a vehicel control (DMSO), arsenic (NaAsO2, 1 uM), BaP (2.5 um) alone or arsenic plus BaP for 30 weeks. At the end of exposure, cells were collected and total RNA was extracted for microarray analysis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE149605 | GEO | 2022/05/18

REPOSITORIES: GEO

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Project description:This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide in vitro to elucidate cancer promoting gene signaling networks (GSNs) associated with As-transformed (B-As) cells. Following a six month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. As exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased ROS protection suggesting mitochondrial dysfunction. Carcinogenic initiation via ROS and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-ÎºB, MAPK and NCOR1 signaling disrupted PPARÎ±/Î´-mediated lipid homeostasis. A âpro-cancerâ GSN identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1Î±, Akt, MAPK, and NF-ÎºB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome GSN profile provide an in vitro As model for future lung cancer signaling research and data for chronic As exposure risk assessment. Whole genome expression profiling was conducted on arsenic (III) oxide-exposed human immortalized lung epithelial cells (BEAS-2B) following 6 month in vitro chronic exposure. As2O3 exposed cells (B-As) gene expression were compared to unexposed, passage control (B-Control) cell gene expression. Three B-As and four B-Control biological replicate cDNA samples were analyzed.

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.

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Microarray analysis of gene expression in human bronchial epithelial cells exposed to arsenic, BaP alone or arsenic plus BaP

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