CARCINOGENESIS OF XENOTRANSPLANTED HUMAN EPITHELIA

异种移植的人类上皮细胞的致癌作用

• 批准号: 3187911
• 负责人: ANDRES J KLEIN-SZANTO
• 金额: $ 9.25万
• 依托单位: FOX CHASE CANCER CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-04-01 至 1988-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3187911
• 关键词: benzanthracenes; carcinoembryonal antigen; chemical carcinogen; chemical carcinogenesis; cytotoxicity; electron microscopy; histochemistry /cytochemistry; human tissue; immunochemistry; respiratory neoplasm; tumor antigens; xenotransplantation

The overall objective of the proposed research is to develop an in vitro experimental model for toxicological and carcinogenesis studies using xenotransplanted-reconstituted human epithelia. Epithelial cells obtained from immediate autopsies of full term fetuses will be isolated and inoculated into deepitehlialized rat tracheas, which will be subsequently sealed, and transplanted subcutaneously into athymic nude mice. The main part of this project comprises the study of normal and carcinogen-treated xenotransplanted-reconstituted human respiratory epithelium. In an initial phase, the kinetics of repopulation of the human xenotransplanted epithelium and the revascularization of the tracheal transplants will be studied in order to ascertain the kinetics of epithelial repopulation as well as to determine the presence of an adequate blood supply. Eventual tumor development as well as other late and early changes induced by 7,12-dimethylbenz(a)anthracene will be studied sequentially during 12-18 months after initiation of exposure. A series of tumor markers of proven clinical or experimental will be studied at different timepoints using smears of tracheal secretions and tissue sections. In the initial phase the following markers will be monitored by histoenzymological and histoimmunochemical techniques: gamma-glutamyl transferase ornithine decarboxylase, carcinoembryonic antigen, ecotopic hormones, loss of blood group antigens and lectin binding. Later other markers such as hematoporphyrin binding, specific anti-lung antibodies etc. could also be investigated. In addition, the in vitro evaluation of altered growth potential of in vivo carcinogen exposed cells will be carried out. Sequential morphological changes will also be evaluated by light microscopy, histometry and transmission electron microscopy.

拟议研究的总体目标是开发一种体外 毒理学和致癌研究的实验模型， 异种移植重建的人类上皮细胞。 获得的上皮细胞 从足月胎儿的立即尸检中分离， 接种到深髓化的大鼠气管中，随后将其 密封并皮下移植到无胸腺裸鼠中。 主要 该项目的一部分包括研究正常和致癌物处理 异种移植重建的人呼吸道上皮。 在初始 阶段，人异种移植的再增殖动力学 上皮和气管移植物的血管重建将是 为了确定上皮细胞再增殖的动力学， 以及确定是否存在足够的血液供应。 最终 肿瘤的发展以及其他晚期和早期的变化引起的 7，12-二甲基苯并（a）蒽将在12-18年期间依次研究 暴露开始后数月。 一系列肿瘤标志物证实 将在不同的时间点进行临床或实验研究， 气管分泌物和组织切片的涂片。 在初始阶段 将通过组织酶学和 组织免疫化学技术：γ-谷氨酰转移酶-鸟氨酸 脱羧酶，癌胚抗原，异位激素，失血 群抗原和凝集素结合。 后来其他标记，如 血卟啉结合、特异性抗肺抗体等也可以 研究了 此外，在体外评估改变的生长 将进行体内致癌物暴露细胞的可能性。 还将通过光镜评价连续形态学变化 显微镜、组织计量学和透射电子显微镜。