GROWTH MODULATORY AND PROMOTERS OF LIVER CANCER II

肝癌生长调节剂和促进剂 II

• 批准号: 3173675
• 负责人: BENITO LOMBARDI
• 金额: $ 10.36万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3173675
• 关键词: cell growth regulation; chemical carcinogen; chemical carcinogenesis; choline; density gradient ultracentrifugation; environment related neoplasm /cancer; histochemistry /cytochemistry; liver neoplasms; nutrition related neoplasm /cancer; nutrition related tag; phenobarbital; radiotracer; scintillation spectrometry

The proposed project is aimed at studying aspects of the mechanism(s) whereby certain environmental factors act as promoters of liver carcinogenesis. Low levels of dietary phenobarbital (PB), or feeding a diet devoid of a single nutritive factor, choline, both strongly promote the induction of liver tumors by chemical carcinogens in rats. Addition of low levels of PB to the choline-devoid (CD) diet results in a synergistic promoting action. Available evidence indicates that the promoters act, basically, by affecting the proliferation of liver target cells, initiated by a chemical carcinogen, and by stimulating their evolution to preneoplastic and neoplastic lesions. These effects could result from the promoters acting directly on the initiated cells, or indirectly, by creating a local micro-environment conducive to the proliferation and evolution of the initiated cells. Normal rat liver contains substances which stimulate or inhibit, respectively, hepatic cell proliferation. The balance between these substances is thought to participate in the regulation of normal liver growth. The studies proposed in this project are designed to gain a better understanding of the nature of these endogenous hepatic substances, and to explore whether and to what extent the liver carcinogenesis promoting action of PB and of a CD diet, either alone or in combination, is mediated by an alteration of the balance of these substances.

拟议的项目旨在研究该机制的各个方面(S) 某些环境因素起到肝脏促进剂的作用 致癌。低水平的饮食苯巴比妥(PB)，或喂养 缺乏单一营养因素的饮食，胆碱，两者都强烈促进 化学致癌物诱发大鼠肝肿瘤的实验研究添加 低水平的铅对无胆碱(CD)饮食产生了协同作用 推动行动。现有证据表明，发起人采取了行动， 基本上，通过影响肝脏靶细胞的增殖，启动 通过一种化学致癌物，并通过刺激它们进化为 癌前病变和肿瘤性病变。这些影响可能是由于 启动子直接作用于被启动的细胞，或通过以下方式间接作用 创造有利于扩散的当地微环境和 启动的细胞的进化。正常大鼠肝脏中含有多种物质 分别刺激或抑制肝细胞增殖。这个 这些物质之间的平衡被认为参与了 调节正常的肝脏生长。本项目中提出的研究 旨在更好地理解这些问题的本质 内源性肝脏物质，并探讨是否和程度 PB和Cd饮食对肝癌的促癌作用 单独或组合，是通过改变平衡来调节的 这些物质。