CHOLINE DEFICIENCY, OVAL CELLS AND HEPATOCARCINOGENESIS

本申请中提出的研究旨在研究以下两个方面 化学性肝癌的发生：1)膳食缺乏对肝癌的影响 单一营养因子，胆碱，对肿瘤的诱导作用；以及，2)性质和 所谓的椭圆形细胞的功能特性。喂食不含胆碱的饮食 已证明对大鼠有促进癌前病变的诱导作用，如 以及肝细胞癌，由几种已知的化学致癌物引起。 提出研究的目的是探讨可能的机制(S)，其中 饮食是肝癌发生的促进剂。应考虑的机制 它们是：1)刺激肝细胞复制；2)饮食和致癌物质 肝细胞膜性质的改变；以及，3)转甲基化 涉及肝细胞大分子甲基化的反应。的影响 此外，还将对饮食对肝癌的启动作用进行研究。在……里面 近年来，人们对胆汁是否有可能 除肝细胞外，导管(球)细胞也可能是化学作用的靶细胞。 在某些情况下，肝细胞癌的致癌物和前体 癌症以及胆管细胞癌。胆管(叶)增生症 随着所谓的椭圆形细胞的出现，细胞是一种常见的早期事件 发生在暴露于化学致癌物的大鼠的肝脏中。研究是 提出旨在实现均相分离的椭圆形制剂 来自致癌物处理大鼠肝脏的细胞；在研究一些 这些细胞的代谢和生物学特性；在探测这些细胞是否 细胞确实在上皮性肝脏肿瘤的发生中扮演了任何角色。

The research proposed in this application is designed to study two aspects of chemical hepatocarcinogenesis: 1) the influence of a dietary deficiency of a single nutritive factor, choline, on tumor induction; and, 2) the nature and functional properties of so-called oval cells. Feeding a diet devoid of choline to rats has been shown to promote the induction of preneoplastic lesions, as well as of hepatocellular carcinomas, by several known chemical carcinogens. Studies are proposed aimed at investigating possible mechanism(s) whereby the diet acts as a promoter of liver carcinogenesis. Mechanisms to be considered are: 1) stimulation of hepatocyte replication; 2) diet and carcinogen-induced changes in the properties of hepatocyte membranes; and, 3) transmethylation reactions involving methylation of hepatocyte macromolecules. The influence of the diet on initiation of liver carcinogenesis will also be investigated. In recent years, a renewed interest has developed about the possibility that bile duct(ular) cells, beside hepatocytes, may also be target cells of chemical hepatocarcinogens, and progenitors, in certain instances, of hepatocellular carcinomas as well as of cholangiocarcinomas. Proliferation of bile duct(ular) cells, with emergence of so-called oval cells, is a common, early event occurring in the liver of rats exposed to chemial carcinogens. Studies are proposed aimed at achieving the isolation of homogeneous preparations of oval cells from the liver of carcinogen-treated rats; at investigating some of the metabolic and biologic properties of these cells; and, at probing whether these cells do indeed play any role in the genesis of epithelial liver tumors.