CHOLINE DEFICIENCY, OVAL CELLS AND HEPATOCARCINOGENESIS

胆碱缺乏、卵圆细胞和肝癌发生

• 批准号: 3166150
• 负责人: BENITO LOMBARDI
• 金额: $ 14.54万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-04-01 至 1986-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3166150
• 关键词: alpha fetoprotein; cell population study; chemical carcinogenesis; electron microscopy; histochemistry /cytochemistry; immunofluorescence technique; liver cells; liver neoplasms; neoplasm /cancer immunology; nutrition aspect of cancer; nutrition related tag; pathogenic diet; preneoplastic state; radioimmunoassay; radiotracer; tissue /cell culture; tissue /cell preparation; tumor promoters; ultracentrifugation

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.

本申请提出的研究旨在研究以下两个方面 化学性肝癌的发生：1）饮食缺乏某种物质的影响 单一营养因子胆碱对肿瘤诱导作用； 2) 性质和 所谓卵圆细胞的功能特性。 饮食中不含胆碱 已证明对大鼠可促进肿瘤前病变的诱导，如 以及肝细胞癌，由几种已知的化学致癌物引起。 提出的研究旨在调查可能的机制，其中 饮食是肝癌发生的促进者。 需要考虑的机制 是：1）刺激肝细胞复制； 2）饮食和致癌物质诱发 肝细胞膜特性的变化；和，3) 甲基转移作用 涉及肝细胞大分子甲基化的反应。 的影响 还将研究饮食对肝癌发生的影响。 在 近年来，人们对胆汁的可能性重新产生了兴趣 除肝细胞外，导管细胞也可能是化学物质的靶细胞 肝癌和祖细胞，在某些情况下，是肝细胞癌 癌以及胆管癌。 胆管（胆管）增生 细胞，即所谓的卵圆细胞的出现，是一种常见的早期事件 发生在接触化学致癌物质的大鼠的肝脏中。 研究是 提出的旨在实现椭圆形均质制剂的分离 来自接受致癌物处理的大鼠肝脏的细胞；在调查一些 这些细胞的代谢和生物学特性；并且，在探究这些是否 细胞确实在上皮性肝肿瘤的发生中发挥作用。