EXPERIMENTAL HEPATOCARCINOGENESIS

抗Novikoff肝癌去组化染色质的抗血清 喂饲致癌物诱发的大鼠原发性肝癌识别 与肿瘤染色质相关且不可检测的各种抗原 在正常、再生或胚胎大鼠的肝脏中。这些抗原中的三个(p39， P49和p56)为细胞角蛋白。这些抗原将是 特征及其与核DNA和核结构的关系 蛋白质(层粘连蛋白、蛋白、染色体支架)由DNA决定 蛋白质和蛋白质：蛋白质交联。抗这些抗体的单抗 我们实验室最近开发的抗原将被用来检测 这些抗原在交联物中的存在。与核糖核酸互补的DNA 针对大鼠癌症的P39抗原将被克隆，并 生成的dna探针将用于研究转录调控。 THIS基因在实验性肝损伤大鼠肝脏中的表达 肝癌的发生。 另一组非常不同的核抗原被表达出来 在化学性肝癌的发生过程中。这些抗原与 核基质制剂。其中几种的单抗 抗原将被用来确定这个复杂的种群是否 抗原是新蛋白质或蛋白质转录表达的结果 抗血清是否识别一种新的翻译后反应 正常大鼠肝脏中蛋白质的修饰。的协会 这些在核基质中含有DNA的蛋白质将被研究 这些抗原在移植瘤中的表达研究 在原发性肝癌的转移性病变中。 我们的主要目标是阐明生物角色， 特异性肝癌相关细胞角蛋白和核基质抗原的作用 在恶性表型的启动、促进和维持方面。 在更实际的方面，我们将利用这些早期出现的 建立检测肿瘤相关抗原的体外方法 具有致癌潜力的化合物。

Antisera to dehistonized chromatins of transplantable Novikoff hepatoma or primary hepatomas produced in rats by feeding hepatocarcinogens recognize a variety of antigens associated with the tumor chromatin and not detectable in normal, regenerating or fetal rat liver. Three of these antigens (p39, p49 and p56) were identified as cytokeratins. These antigens will be characterized and their relationships to nuclear DNA and nuclear structural proteins (lamins, matricins, chromosomal scaffolds) determined by DNA protein and protein:protein crosslinking. Monoclonal antibodies to these antigens, developed recently in our laboratory, will be used to detect the presence of these antigens in the crosslinks. DNA complementary to mRNA of the p39 antigen which is specific for rat carcinomas will be cloned and the resulting DNA probes will be used to study the transcriptional regulation of th is gene in livers of rats subjected to experimental hepatocarcinogenesis. Another, very heterogeneous, group of nuclear antigens becomes expressed during chemical hepatocarcinogenesis. These antigens are associated with nuclear matrix preparations. Monoclonal antibodies to several of these antigens will be used to determine whether this complex population of antigens is the result of transcriptional expression of new proteins or whether the antisera recognize a new kind of post-translational modification of proteins present in normal rat liver. The associations of these proteins with DNA in the nuclear matrix will be investigated along with studies on the expression of these antigens in transplantation tumors and in metastases of the primary hepatocarcinomas. Our principal aims are the elucidation of biological roles which the specific hepatoma associated cytokeratins and nuclear matrix antigens play in the initiation, promotion and maintenance of the malignant phenotype. In a more practical aspect, we will utilize the early appearance of these tumor-associated antigens to develop an in vitro assay for the detection of compounds with carcinogenic potential.