GENETIC DETERMINANTS IN CHEMICAL HEPATOCARCINOGENESIS

这个项目的主要目标是定义遗传决定因素 关于肝癌发生和随后演变的初始阶段 由化学致癌物和其他物质引起的肝脏肿瘤 致癌物质。大鼠肝脏发生的主要病变 作为启动-促进协议的结果是改变的焦点 肝细胞。由多种致癌物引起的这些病灶 已被证明遵循明显的一级剂量反应，表明 病灶是启动的细胞的克隆性扩张。因此 启蒙的表型应该完全表现为 改变的肝细胞。为了验证这一假设，我们开始了一系列 激活的逆转录病毒相关癌基因是 将其导入非致瘤大鼠肝上皮细胞系 原代培养大鼠肝细胞，并测定其表型变化。这个 目前的研究主要集中在：(1)转染大鼠肝细胞 逆转录病毒相关癌基因，(2)逆转录病毒的构建 基于载体的转导系统将选定的癌基因导入 原代肝细胞的表达；(3)正常肝细胞和正常肝细胞c DNA文库的构建 肿瘤大鼠肝脏。

The main objective of this project is to define the genetic determinants for the initiation stage in hepatocarcinogenesis and subsequent evolution of liver tumors that are brought about by chemical carcinogens and other cancer causing agents. The principal lesions that develop in the rat liver as a result of initiation-promotion protocols are foci of altered hepatocytes. Initiation of these foci by a variety of hepatocarcinogens has been shown to follow an apparent first order dose response, suggesting that the foci are a clonal expansion of the initiated cell. Consequently the phenotype of initiation should be completely represented by the foci of altered hepatocytes. To test this hypothesis we have started a series of experiments in which activated retroviral-associated oncogenes are transfected into a nontumorigenic rat liver epithelial cell line and primary rat hepatocytes, and the phenotypic changes determined. The research is currently focused on: (1) transfecting rat liver cells with retroviral associated oncogenes, (2) construction of a retroviral vector-based transfection system to introduce selected oncogenes into primary hepatocytes, and (3) construction of cDNA libraries from normal and neoplastic rat liver.