Tobacco Carcinogen Oral Cancer Model

烟草致癌物口腔癌模型

• 批准号: 6950796
• 负责人: Joel L Schwartz
• 金额: $ 7.75万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6950796
• 关键词: arecoline; benzopyrenes; cancer prevention; carcinogens; chemical carcinogenesis; chemical related neoplasm /cancer; disease /disorder model; hamsters; model design /development; mouth neoplasms; nitrosamines; oral mucosa; oral pharyngeal neoplasm; tobacco

DESCRIPTION (provided by applicant): In the United States there are about 30,000 new oral cancer cases per year. Oral cancer is often associated with tobacco product use but current prevention methods to reduce numbers of new cases are ineffective. An oral cancer model paralleling human exposure to tobacco carcinogens is expected to enhance our ability to prevent oral cancer. Exisiting oral cancer models have generally relied upon synthetic carcinogens minimizing parallels to human exposure experience and changes in oral mucosa. Other environmental agents, tobacco specific N-nitrosamines, or arecoline derived from the betal nut either lack the ability to initiate oral carcinogenesis or have not been evaluated extensively for cell biology mechanisms. Few oral carcinogenesis studies have examined the cellular events in the oral keratincyte following exposure to tobacco carcinogen. Our goal is to establish a tobacco carcinogen induced oral carcinogenesis model, which can be replicated by others for prevention of oral cancer. This model will have a high tumor incidence and multiplicity after a relatively short period of induction. Tumor induction in tongue and floor of the mouth will parallel sites in humans. This model will also be extendable to other models such as the guinea pig and knock-out mouse to study prevention. Environmental and tobacco carcinogens, fjord structured, dibenzo[a,I]pyrene, diB[a,I]P will be compared to a bay region chemical, benzo[a]pyrene, B[a]P, an established oral carcinogen in the hamster. In a preliminary study, diB[a,I]P was observed to be a more potent carcinogen than B[a]P. This result requires confirmation which we will obtain from the following studies: Aim la. A dose response effect for diB[a,I]P/B[a]P assessing tumor incidence and multiplicity. lb. Detection of DNA adduct type and presence in histologic sites and p53 mutations during oral carcinogenesis. lc. Assessments of membrane (aryl hydrolase) and cytoplasmic phase I and II enzymes. ld. Confirmation of early cellular initiation and promotion events critical to our understanding for prevention of oral cancer.

描述（由申请人提供）： 在美国，每年约有 30,000 例新发口腔癌病例。口腔癌通常与烟草产品的使用有关，但目前减少新病例数量的预防方法是无效的。与人类接触烟草致癌物平行的口腔癌模型有望增强我们预防口腔癌的能力。现有的口腔癌模型通常依赖于合成致癌物，最大限度地减少与人类暴露经历和口腔粘膜变化的相似性。其他环境因素、烟草特有的 N-亚硝胺或源自甜菜的槟榔碱要么缺乏引发口腔癌的能力，要么尚未对其细胞生物学机制进行广泛评估。很少有口腔致癌研究检查接触烟草致癌物后口腔角质细胞的细胞事件。我们的目标是建立烟草致癌物诱发的口腔癌模型，可供其他人复制以预防口腔癌。该模型在相对较短的诱导期后将具有较高的肿瘤发生率和多样性。舌头和口底的肿瘤诱导将与人类的平行部位相同。该模型还可扩展到其他模型，例如豚鼠和基因敲除小鼠，以研究预防。环境和烟草致癌物、峡湾结构、二苯并[a,I]芘、diB[a,I]P 将与湾区化学品苯并[a]芘、B[a]P 进行比较，苯并[a]芘、B[a]P 是海湾地区已确定的口腔致癌物。仓鼠。在一项初步研究中，观察到 diB[a,I]P 是比 B[a]P 更强的致癌物质。这一结果需要我们从以下研究中获得证实：Aim la。 diB[a,I]P/B[a]P 的剂量反应效应评估肿瘤发生率和多重性。 lb.口腔癌发生过程中DNA加合物类型和组织学位点的存在以及p53突变的检测。 LC。膜（芳基水解酶）和细胞质 I 相和 II 相酶的评估。 ld。确认早期细胞启动和促进事件对于我们了解预防口腔癌至关重要。