SEQUENTIAL ANALYSIS OF ORAL CARCINOGENESIS

口腔癌发生的序贯分析

• 批准号: 3171934
• 负责人: Dennis B. Solt
• 金额: $ 7.4万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-07-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3171934
• 关键词: autoradiography; benzanthracenes; cellular oncology; chemical carcinogenesis; cytotoxicity; dosage; microscopy; mouth neoplasms; nutrition related tag; oral pharyngeal neoplasm; radionuclides; tissue /cell preparation

The long-range objective of the proposed research is to identify and analyze in sequential fashion, the key pathological changes occurring during oral carcinogenesis. Full thickness whole mounts and viable single cell dissociates of carcinogen treated hamster buccal pouch epithelium (HBPE) will be examined for histochemical, morphological and functional evidence of cells which have undergone one or more steps in the carcinogenic process. Emphasis will be placed on the role of carcinogen induced HBPE cells with histochemical activity for gamma-glutamyl transpeptidase (GGT), a marker for presumptive initiation sites in this model. The specific aims are: 1) to characterize the GGT+ sites with regard to their (a) origin in individual replicating cells, (b) resistance to cytotoxicity, and (c) persistence; 2) to evaluate the potential of 2,3,7,8-tetrachlorodibenzo-p-dioxin to serve as a promoting agent for HBPE; 3) to enzymatically dissociate initiated HBPE and determine whether the isolated cells manifest (a) an enhanced capacity for survival and growth in vitro, (b) altered differentiation in vitro, and (c) angiogenic and tumorigenic potential. This research is based on the premise that improved strategies for the early detection or prevention of oral cancer will require a thorough familiarity with the phenotypic properties of precancerous oral lesions and a detailed knowledge of the mechanisms involved in their induction and subsequent evolution to cancer.

拟议研究的长期目标是确定和 按顺序分析发生的关键病变， 在口腔癌发生过程中。 全厚度整体安装和可行的单 致癌剂处理的仓鼠颊囊上皮细胞分离物 （HBPE）将进行组织化学、形态学和功能检查 细胞经历了一个或多个步骤， 致癌过程 重点将放在致癌物的作用 具有γ-谷氨酰组织化学活性的诱导HBPE细胞 转肽酶（GGT），这是一个假定的起始位点的标志物， 模型 具体目标是：1）表征GGT+位点， 关于它们的（a）起源于单个复制细胞，（B）抗性 细胞毒性，和（c）持久性; 2）评价 2，3，7，8-四氯二苯并-p-二恶英作为HBPE的促进剂; 3)以酶促解离引发的HBPE并确定所述HBPE是否 分离的细胞表现出（a）增强的存活和生长能力， 体外，（B）体外改变的分化，和（c）血管生成和 致瘤潜力 这项研究的前提是， 早期发现或预防口腔癌的策略将 需要彻底熟悉的表型特性， 口腔癌前病变和机制的详细知识 参与了它们的诱导和随后的癌症演变。