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Nicotine increases oxidative stress, activates NF-κB and GRP78, induces apoptosis and sensitizes cells to genotoxic/xenobiotic stresses by a multiple stress inducer, deoxycholate: relevance to colon carcinogenesis

Epidemiologic studies indicate that environmental (smoking) and dietary factors (high fat) contribute to carcinogenesis in many organ systems. The aim of our study was to test the hypothesis that nicotine, a component of cigarette smoke, and sodium deoxycholate (NaDOC), a cytotoxic bile salt that in...

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Bibliographic Details
Published in:Chemico-biological interactions 2003-03, Vol.145 (1), p.53-66
Main Authors: Crowley-Weber, Cara L, Dvorakova, Katerina, Crowley, Cheray, Bernstein, Harris, Bernstein, Carol, Garewal, Harinder, Payne, Claire M
Format: Article
Language:English
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Summary:Epidemiologic studies indicate that environmental (smoking) and dietary factors (high fat) contribute to carcinogenesis in many organ systems. The aim of our study was to test the hypothesis that nicotine, a component of cigarette smoke, and sodium deoxycholate (NaDOC), a cytotoxic bile salt that increases in concentration in the gastrointestinal tract after a high fat meal, induce similar cellular stresses and that nicotine may enhance some of the NaDOC-induced stresses. We found that nicotine, at 0.8 μM, the very low sub-micromolar level occurring in the tissues of smokers: (1) increases oxidative stress; (2) activates NF-κB, a redox-sensitive transcription factor; (3) activates the 78 kD glucose regulated protein promoter, an indication of endoplasmic reticulum stress; (4) induces apoptosis; (5) enhances the ability of NaDOC to activate the 153 kD growth arrest and DNA damage promoter, an indication of increased genotoxic stress; and (6) enhances the ability of NaDOC to activate the xenobiotic response element. Our findings have applicability to G.I. cancer, in general, since smoking is a risk factor in the development of esophageal, pancreatic, gastric and colon cancer, and these cancers are also promoted by bile acids.
ISSN:0009-2797
1872-7786
DOI:10.1016/S0009-2797(02)00162-X