MUCOSAL PERMEABILITY AND SMOKELESS TOBACCO COMPONENTS

最近，该词的使用显著增加，尤其是 在年轻人中，一些形式的无烟烟草 (嚼烟草和鼻烟)在美国。还有就是 越来越多的流行病学和临床证据表明，当地和 与这种习惯相关的系统性病理效应仍存在 很少有实验研究。无烟烟草通常是 放置在口腔粘膜表面，很少被摄取，所以 它的作用必须几乎完全通过口腔来实现 粘膜衬里。这项研究方案考虑了 渗透率和某些成分的渗透率之间的关系 无烟烟草横跨口腔粘膜以及直接 对粘膜的影响。具体而言，该项目将审查(A) 角化型和非角化型的渗透性屏障的化学性质 口腔非角化区，(B)唾液粘蛋白的作用 至渗透性屏障功能，(C)渗透率 烟草相关成分，尼古丁和致癌物， 这些不同地区的亚硝胺或尼古丁(NNN)(D) 这些组分之间的相互作用和乙醇的影响 关于NNN在口腔粘膜中的渗透性，以及(E) 尼古丁对口腔粘膜的形态影响。通透性 猪口腔黏膜不同区域的屏障将是 通过量化脂类、糖脂的相对数量进行检查 和上皮特定组织层中的糖蛋白。 用薄层层析法和十二烷基硫酸钠-聚丙烯酰胺凝胶 电泳法。烟草成分的渗透率，神经网络 和尼古丁，将通过测定渗透率来确定 使用放射性标记的相同粘膜区域的常数 化合物。将检查形态和病理效应 在猪组织体外和在体大鼠体内，利用光和 电子显微镜。 这些研究代表了对 口腔黏膜屏障功能与口腔粘膜功能的关系 烟草成分对组织的渗透和影响。 这项工作对健康的影响也远远超出了 无烟烟草，因为还有其他物质，如酒精 而亚硝胺存在于许多食物中，这可能是 如果它们穿透口腔衬里，就会引发口腔疾病。

There has recently been a marked increase in the use, particularly among young people, of some forms of smokeless tobacco (chewing tobacco and snuff) in the United States. There is also increasing epidemiologic and clinical evidence of local and systemic pathologic effects associated with this habit yet there are few experimental studies. Smokeless tobacco is customarily placed on the surface of the oral mucosa, and rarely ingested, so that its effects must be mediated almost entirely via the oral mucosal lining. This research proposal considers the relationship between permeability and the penetration of certain components of smokeless tobacco across the oral mucosa as well as the direct effects on the mucosa. Specifically, the project will examine (a) the chemical nature of the permeability barrier in keratinized and nonkeratinized oral regions, (b) the contribution of salivary mucin to permeability barrier function, (c) the penetration of the tobacco associated components, nicotine and the carcinogen, nitrosonornicotine (NNN) across these different regions (d) the effect of interactions between these components and of ethanol on the penetration of NNN across oral mucosa, and (e) the morphologic effects of nicotine on oral mucosa. The permeability barrier in different regions of porcine oral mucosa will be examined by quantifying the relative amounts of lipids, glycolipids and glycoproteins in specific histologic strata of the epithelia using thin layer chromatography and SDS-polyacrylamide gel electrophoresis. Penetration of the tobacco components, NNN and nicotine, will be determined by determining permeability constants for the same mucosal regions using radiolabelled compounds. Morphologic and pathologic effects will be examined in porcine tissue in vitro and in rats in vivo, using light and electron microscopy. These studies represent a comprehensive investigation of the relationship between oral mucosal barrier function and the penetration and effects of components of tobacco on the tissues. The work also has health implications extending well beyond smokeless tobacco, for there are other substances, such as alcohol and the nitrosamines present in many foodstuffs, that may be capable of initiating oral disease if they penetrate the oral lining.