Project description:Temporal analysis of the effect of cigarette smoke on normal human bronchial epithelial cells (NHBE), and S9 toxicity. Keywords: other
Project description:normal human bronchial epithelial cultures from two cultures in parallel exposed to cigarette smoke (CS) or air (mock) at timepoints 4 hours and 24 hours. Keywords = cigarette smoke Keywords = microarray Keywords = bronchial cell Keywords = tobacco Keywords: time-course
Project description:Nine cigarette smoke condensates (CSCs) were produced under a standard ISO smoking machine regimen and one was produced by a more intense smoking machine regimen. These CSCs were used to treat primary normal human bronchial epithelial cells for 18 hours. Experiment Overall Design: Primary human bronchial/tracheal epithelial cells were grown in culture and treated with 10 different sources of cigarette smoke condensates.
Project description:Exposure to cigarette smoke is a leading cause of lung diseases including chronic obstructive pulmonary disease and cancer. Cigarette smoke is a complex aerosol containing over 6000 chemicals, and thus it is difficult to determine individual contributions to overall toxicity, and the molecular mechanisms by which smoke constituents exert their effects. We selected three well-known harmful and potentially harmful constituents (HPHCs) in tobacco smoke: acrolein, formaldehyde and catechol and established a High Content Screening (HCS) method using normal human bronchial epithelial cells, which are the first bronchial cells in contact with cigarette smoke. The impact of each HPHC was investigated using 13 multi-parametric indicators of cellular toxicity and complemented with a microarray-based whole transcriptome analysis followed by a computational approach leveraging mechanistic network models to identify and quantify perturbed molecular pathways. HPHCs were evaluated over a wide range of concentrations and at different exposure time points (4 h, 8 h, and 24 h). By High Content Screening, the toxic effects of the three HPHCs could only be observed at the highest doses. Whole genome transcriptomics unraveled toxicity mechanisms at lower doses and earlier time points. The most prevalent toxicity mechanisms observed were: DNA damage/growth arrest, oxidative stress, mitochondrial stress and apoptosis/necrosis. In summary, combination of multiple toxicological endpoints with a systems-based impact assessment allows for a more robust scientific basis for the toxicological assessment of HPHCs that allows insight into time- and dose-dependent molecular perturbations of specific biological pathways. This approach allowed us to establish an in vitro Systems Toxicology platform that can be applied to a broader selection of HPHCs and their mixtures and can serve more generally as the basis for testing the impact of other environmental toxicants on normal bronchial epithelial cells.
Project description:This SuperSeries is composed of the following subset Series:; GSE14383: Effects of chronic exposure of human bronchial epithelial cells to low doses of cigarette smoke condensate; GSE14385: Response of bronchial epithelial cells to low doses of cigarette smoke condensate and subsequent demethylation agent Experiment Overall Design: Refer to individual Series
Project description:Gene expression patterns were assessed in normal human bronchial epithelial (NHBE) cells exposed to cigarette smoke from a reference cigarette (2R4F, University of Kentucky) and a typical American brand of "light" cigarettes ("Lights") in order to develop a better understanding of the genomic impact of tobacco exposure, which can ultimately define biomarkers that discriminate tobacco-related effects and outcomes in a clinical setting. NHBE cells were treated with whole cigarette smoke for 15 minutes and alterations to the transcriptome assessed at 2, 4, 8 and 24 hours post-exposure using high-density oligonucleotide microarrays. Keywords: time course, cigarette smoke exposure
Project description:Nine cigarette smoke condensates (CSCs) were produced under a standard ISO smoking machine regimen and one was produced by a more intense smoking machine regimen. These CSCs were used to treat primary normal human bronchial epithelial cells for 18 hours.
Project description:MicroRNA expression was assayed from bronchial epithelial cells collected via bronchoscopy from healthy current and never smoker volunteers in order to determine the effect of cigarette smoke exposure on airway epithelial microRNA expression Keywords: Global microRNA expression profiling
Project description:This study was performed to test the hypothesis that cigarette smoke extract would alter the responses of primary cultures of human bronchial epithelial cells to infection with purified human rhinovirus 16. The data show marked alterations in rhinovirus-induced expression profiles of a number of genes in the presence of cigarette smoke extract (CSE).
