Abstract |
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 microM, the very low sub-micromolar level occurring in the tissues of smokers: (1). increases oxidative stress; (2). activates NF-kappaB, 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.
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Authors | Cara L Crowley-Weber, Katerina Dvorakova, Cheray Crowley, Harris Bernstein, Carol Bernstein, Harinder Garewal, Claire M Payne |
Journal | Chemico-biological interactions
(Chem Biol Interact)
Vol. 145
Issue 1
Pg. 53-66
(Mar 06 2003)
ISSN: 0009-2797 [Print] Ireland |
PMID | 12606154
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- CCAAT-Enhancer-Binding Proteins
- Carrier Proteins
- DDIT3 protein, human
- Endoplasmic Reticulum Chaperone BiP
- HSPA5 protein, human
- Heat-Shock Proteins
- Molecular Chaperones
- Mutagens
- NF-kappa B
- Transcription Factors
- Xenobiotics
- Deoxycholic Acid
- Transcription Factor CHOP
- Nicotine
- Chloramphenicol O-Acetyltransferase
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Topics |
- Apoptosis
(drug effects)
- CCAAT-Enhancer-Binding Proteins
(genetics)
- Carrier Proteins
(metabolism)
- Chloramphenicol O-Acetyltransferase
(genetics)
- Colonic Neoplasms
(chemically induced, pathology)
- DNA Damage
- Deoxycholic Acid
(toxicity)
- Endoplasmic Reticulum Chaperone BiP
- Enzyme-Linked Immunosorbent Assay
- Heat-Shock Proteins
- Humans
- Membrane Potentials
(drug effects)
- Molecular Chaperones
(metabolism)
- Mutagens
(toxicity)
- NF-kappa B
(metabolism)
- Nicotine
(pharmacology)
- Oxidative Stress
(drug effects)
- Promoter Regions, Genetic
- Transcription Factor CHOP
- Transcription Factors
(genetics)
- Tumor Cells, Cultured
- Xenobiotics
(toxicity)
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