Bagchi M, Bagchi D, Adickes E, Stohs S J
Department of Pharmaceutical and Administrative Sciences, Creighton University Health Sciences Center, Omaha, NE 68178, USA.
J Environ Pathol Toxicol Oncol. 1995;14(2):61-8.
Tobacco consumption is a worldwide problem. The recent increase in the consumption of the smokeless tobacco products (snuff and chewing tobacco) has stimulated interest into the carcinogenic effects of these forms of tobacco. The use of smokeless tobacco products has increased in popularity as the use of cigarettes has become less socially acceptable. For most individuals the use of tobacco is a chronic process. Therefore, the effects of an aqueous extract of smokeless tobacco (STE) in rats following low-dose exposure were examined. Female Sprague-Dawley rats were treated orally with 25 mg STE/kg every other day for 90 days. In order to obtain information regarding the cytotoxicity of STE, the ultrastructural changes occurring in livers of rats following administration of STE were examined under light and electron microscopy. Electron microscopy revealed that in the perisinusoidal spaces an accumulation of indistinct filamentous material occurred following 60 days of treatment, occupying most of the sinusoids. Moreover, the lipids were in a state of disintegration. Significant increases in 90 kDa protein expression were also observed due to chronic treatment with STE. Western blot analysis using a polyclonal mouse antibody against heat shock/stress protein 90 (HSP90) confirmed that the overexpressed proteins were heat shock/stress proteins (HSPs). The HSPs are believed to serve as adaptive or survival functions involving a rapid but transient reprogramming of cellular metabolic activity to protect cells from oxidative damage.
烟草消费是一个全球性问题。近期无烟烟草产品（鼻烟和嚼烟）消费的增加引发了人们对这些烟草形式致癌作用的关注。随着香烟使用在社会上变得越来越不可接受，无烟烟草产品的使用越来越普遍。对大多数人来说，烟草使用是一个慢性过程。因此，研究了低剂量接触后无烟烟草水提取物（STE）对大鼠的影响。雌性斯普拉格-道利大鼠每隔一天口服25毫克STE/千克，持续90天。为了获取有关STE细胞毒性的信息，在光学显微镜和电子显微镜下检查了STE给药后大鼠肝脏中发生的超微结构变化。电子显微镜显示，治疗60天后，在窦周间隙出现了不清晰丝状物质的积累，占据了大部分肝血窦。此外，脂质处于解体状态。由于长期用STE治疗，还观察到90 kDa蛋白表达显著增加。使用针对热休克/应激蛋白90（HSP90）的多克隆小鼠抗体进行的蛋白质印迹分析证实，过表达的蛋白是热休克/应激蛋白（HSPs）。HSPs被认为具有适应性或生存功能，涉及细胞代谢活动的快速但短暂的重新编程，以保护细胞免受氧化损伤。
