MUCOSAL PERMEABILITY AND SMOKELESS TOBACCO COMPONENTS

最近，使用量明显增加，特别是 在年轻人中，某些形式的无烟烟草 （嚼烟草和鼻烟）在美国。 还有 越来越多的流行病学和临床证据表明， 与这种习惯相关的全身性病理影响， 很少有实验研究。 无烟烟草通常 放置在口腔粘膜表面，很少摄入，所以 它的作用必须几乎完全通过口腔介导， 粘膜内层 该研究建议考虑了 渗透性和某些成分的渗透性之间的关系 无烟烟草对口腔粘膜的影响以及 对粘膜的影响。 具体而言，该项目将审查（a） 角质化和角质化皮肤中渗透屏障的化学性质 非角化的口腔区域，（B）唾液粘蛋白的贡献 渗透屏障功能，（c）渗透的 烟草相关成分、尼古丁和致癌物质， （d）在这些不同区域的亚硝基去甲烟碱（NNN） 这些组分和乙醇之间相互作用的影响 对NNN穿过口腔粘膜的渗透的影响，以及（e） 尼古丁对口腔粘膜的形态学影响。 渗透率 猪口腔粘膜不同区域的屏障， 通过定量脂质、糖脂 和糖蛋白在上皮细胞的特定组织层中 采用薄层色谱和SDS-聚丙烯酰胺凝胶 电泳 烟草成分的渗透率，NNN 和尼古丁，将通过测定渗透性来确定 使用放射性标记的相同粘膜区域的常数 化合物. 将检查形态学和病理学影响 在体外猪组织和在体内大鼠中，使用光和 电镜 这些研究代表了一个全面的调查， 口腔黏膜屏障功能与口腔黏膜损伤的关系 渗透和烟草成分对组织的影响。 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 以及许多食品中存在的亚硝胺， 如果它们穿透口腔内层，能够引发口腔疾病。

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.