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Investigation into the effects of the tobacco smoke procarcinogen benzo[a]pyrene on gene expression profiles in oesophageal cancer

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dc.contributor.advisor Parker MI, Prof en
dc.contributor.author Bick AJ en
dc.date.accessioned 2016-09-22T09:15:44Z
dc.date.available 2016-09-22T09:15:44Z
dc.date.submitted 2011 en
dc.identifier.uri http://hdl.handle.net/20.500.11892/51287
dc.description.abstract Tobacco smoking is a major risk factor in the development of oesophageal squamous cell carcinoma (OSCC). Benzo[a]pyrene (BaP) is a tobacco smoke procarcinogen that is metabolically activated into the carcinogenic benzo[a]pyrene diol-epoxide (BPDE) by the CYP1 family of cytochrome P450 enzymes. BaP is a ligand for the aryl hydrocarbon receptor (AhR) which activates CYP1 gene transcription. Polymorphisms in these genes affect enzyme activity and therefore BaP bioactivation. The effects of BaP on expression of CYP1A1, CYP1B1 and the AhR and cell proliferation were compared between a normal oesophageal epithelial cell line (EPC-2) and an OSCC cell line (WHCO1). Transcriptional profiling of the effects of BaP treatment on global gene expression in WHCO1 and EPC-2 cells was carried out using an Illumina microarray system and the data analyzed using Ingenuity Pathways Analysis (IPA) software. Treatment with BaP induced CYP1A1 and CYP1B1 mRNA and protein to a greater extent in WHCO1 compared to EPC-2 cells, and their levels remained elevated when BaP was removed. Nuclear translocation and exit of AhR and ARNT was more rapid in EPC-2 cells during BaP treatment and withdrawal than in WHCO1 cells. Genes involved in inflammation and xenobiotic metabolism were differentially expressed in WHCO1 cells, while genes involved in cell cycle regulation and the DNA damage response were differentially expressed in EPC-2 cells. These results suggest that WHCO1 cells are more efficient at CYP1 induction and therefore BaP bioactivation than normal cells. Prolonged CYP1 induction and nuclear AhR-ARNT signaling events in WHCO1 cells may contribute to cancer maintenance or promotion, while reduced CYP1 induction in EPC-2 cells may result in less efficient BaP detoxification and subsequent accumulation of DNA-damaging metabolites which cause reduced cell proliferation to allow for DNA repair. en
dc.language English en
dc.subject Medical sciences: Diseases en
dc.title Investigation into the effects of the tobacco smoke procarcinogen benzo[a]pyrene on gene expression profiles in oesophageal cancer en
dc.type Masters degree en
dc.description.degree MSc (Med) en

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