CARCINOGENESIS OF XENOTRANSPLANTED HUMAN EPITHELIA

这项拟议研究的总体目标是开发一种体外 用于毒理学和致癌研究的实验模型 异种移植-重组人上皮。获得上皮细胞 从足月胎儿的直接尸检中分离出来 接种到深厚的大鼠气管内，随后将 密封，并移植到裸鼠的皮下。主 该项目的一部分包括正常和致癌物治疗的研究。 异种移植重组人呼吸道上皮。在首字母中 人异种移植后再繁殖的动力学研究 气管移植的上皮和血运重建将是 研究以确定上皮细胞再繁殖的动力学为 以及确定是否存在足够的血液供应。最终 肿瘤的发展及其他晚期和早期变化 7，12-二甲基苯并(A)蒽将在12-18年间连续研究 在暴露开始后的几个月。一系列已被证实的肿瘤标志物 临床或实验将在不同的时间点进行研究，使用 气管分泌物和组织切片的涂片。在初始阶段 下列标记将通过组织酶学和 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、生态激素、失血 组抗原和凝集素结合。后来，其他标记，如 血卟啉结合、特异性抗肺抗体等也可以 调查过了。此外，改变生长的体外评价 体内致癌物暴露细胞的潜力将被开展。 连续的形态变化也将通过光来评估 显微镜、组织计量学和透射电子显微镜。

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.