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：1）饮食中缺乏 单一营养因子胆碱对肿瘤诱导的影响; 2）肿瘤的性质和 所谓的卵圆细胞的功能特性。 饮食中缺乏胆碱 已经显示出促进肿瘤前病变的诱导， 以及肝细胞癌，几种已知的化学致癌物。 建议开展研究，以调查可能的机制， 饮食可作为肝癌发生的促进剂。 有待考虑的机制 是：1）刺激肝细胞复制; 2）饮食和致癌物诱导 肝细胞膜性质的改变;和，3）转甲基化 肝细胞大分子甲基化反应。 的影响 还将研究饮食对肝癌发生的起始作用。 在 近年来，人们对胆汁 除了肝细胞外，导管细胞也可能是化学药物的靶细胞。 肝致癌物和肝细胞的祖细胞，在某些情况下， 癌以及胆管癌。 胆管增生（ular） 细胞，出现所谓的卵圆细胞，是一种常见的早期事件， 发生在暴露于化学致癌物的大鼠肝脏中。 研究是 提出的目的是实现分离的均匀制剂的椭圆形 从致癌物处理的大鼠的肝脏细胞;在研究一些 这些细胞的代谢和生物学特性;并且，在探测这些细胞是否 细胞确实在上皮性肝肿瘤的发生中起任何作用。

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.