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
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
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DOI：
10.1016/s0009-2797(02)00162-x
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发表时间：
2003-03-06
影响因子：
5.1
通讯作者：
Payne, CM
中科院分区：
文献类型：
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作者：
Crowley-Weber, CL;Dvorakova, K;Payne, CM
表皮学研究表明，环境（吸烟）和饮食因素（高脂肪）有助于许多器官系统的致癌作用。我们研究的目的是检验以下假设：尼古丁（香烟烟雾的一种成分）和脱氧胆酸钠（NaDOC）（一种细胞毒性胆汁盐，在高脂餐后胃肠道中浓度增加）诱导类似的细胞应激，尼古丁可能会增强某些NaDOC诱导的应激。我们发现，0.8 μ M的尼古丁，即吸烟者组织中非常低的亚微摩尔水平：（1）增加氧化应激;（2）激活NF-κ B，一种氧化还原敏感的转录因子;（3）激活78 kD葡萄糖调节蛋白启动子，一种内质网应激的指示;（4）诱导细胞凋亡;（5）增强NaDOC激活153 kD生长停滞和DNA损伤启动子的能力，这是增加的遗传毒性胁迫的指示;和（6）增强NaDOC激活异生素反应元件的能力。我们的研究结果适用于G.I.一般来说，吸烟是癌症的主要危险因素，因为吸烟是食道癌、胰腺癌、胃癌和结肠癌的危险因素，而胆汁酸也会促进这些癌症的发生。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Epidermiologic 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 muM, 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. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.