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A platform for research: civil engineering, architecture and urbanism
Proteomic Analysis of Benzo[a]pyrene-Mediated Bladder Toxicity
The major objective of this study was to evaluate whether the environmental contaminant benzo[a]pyrene B[a]P, one of the most important polycyclic aromatic hydrocarbons (PAH), is capable of mediating DNA damage in urinary bladder epithelial cells and hence potentially bladder carcinogenesis. To pursue this goal, effects of B[a]P on urinary bladder epithelial cells were investigated by applying a proteomic approach with the purpose of identifying proteins and pathways involved in B[a]P toxicity. First, the ability of bladder epithelial cells for B[a]P uptake and metabolism was determined. Secondly, a proteome map of primary porcine urinary bladder epithelial cells (PUBEC), the cell model used in the majority of the studies, was established as basis for comparative investigations. In the same model, investigations on time- and concentration-dependent expression changes of proteins after B[a]P exposure followed. The proteins were separated by using 2D gel electrophoresis and identified by MALDI-TOF-MS analysis in these studies. Finally, to elucidate mechanisms by which B[a]P mediates its toxicity, signaling pathways were studied in RT4 cells by using Blue Native PAGE analysis. Besides offering some insights into B[a]P-mediated toxic effects, the studies also point towards the possibility of bladder cancer development induced by B[a]P exposure. B[a]P is a ubiquitous environmental pollutant formed during the combustion of fossil fuels, grilling, barbecuing, and smoking of food. Although much information is available on the carcinogenic properties of B[a]P, the mechanism by which this chemical is taken up by cells is still not known. In Chapter 3 of this thesis, attempts were made to investigate the dynamics of B[a]P uptake, subcellular distribution, and metabolism in PUBEC. It was found that exposure to 0.5 μM B[a]P led to an increase in intracellular concentration of B[a]P in bladder epithelial cells in a time-dependent manner but without approaching saturation. Also, a marked difference in B[a]P uptake was observed ...
Proteomic Analysis of Benzo[a]pyrene-Mediated Bladder Toxicity
The major objective of this study was to evaluate whether the environmental contaminant benzo[a]pyrene B[a]P, one of the most important polycyclic aromatic hydrocarbons (PAH), is capable of mediating DNA damage in urinary bladder epithelial cells and hence potentially bladder carcinogenesis. To pursue this goal, effects of B[a]P on urinary bladder epithelial cells were investigated by applying a proteomic approach with the purpose of identifying proteins and pathways involved in B[a]P toxicity. First, the ability of bladder epithelial cells for B[a]P uptake and metabolism was determined. Secondly, a proteome map of primary porcine urinary bladder epithelial cells (PUBEC), the cell model used in the majority of the studies, was established as basis for comparative investigations. In the same model, investigations on time- and concentration-dependent expression changes of proteins after B[a]P exposure followed. The proteins were separated by using 2D gel electrophoresis and identified by MALDI-TOF-MS analysis in these studies. Finally, to elucidate mechanisms by which B[a]P mediates its toxicity, signaling pathways were studied in RT4 cells by using Blue Native PAGE analysis. Besides offering some insights into B[a]P-mediated toxic effects, the studies also point towards the possibility of bladder cancer development induced by B[a]P exposure. B[a]P is a ubiquitous environmental pollutant formed during the combustion of fossil fuels, grilling, barbecuing, and smoking of food. Although much information is available on the carcinogenic properties of B[a]P, the mechanism by which this chemical is taken up by cells is still not known. In Chapter 3 of this thesis, attempts were made to investigate the dynamics of B[a]P uptake, subcellular distribution, and metabolism in PUBEC. It was found that exposure to 0.5 μM B[a]P led to an increase in intracellular concentration of B[a]P in bladder epithelial cells in a time-dependent manner but without approaching saturation. Also, a marked difference in B[a]P uptake was observed ...
Proteomic Analysis of Benzo[a]pyrene-Mediated Bladder Toxicity
Verma, Nisha (author) / Rettenmeier, Albert W.
2013-01-28
Theses
Electronic Resource
English
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