PATHOBIOLOGY OF HIGH DOSE SUCROSE PROMOTION IN THE RAT

高剂量蔗糖促进大鼠的病理学

• 批准号: 3188940
• 负责人: OSCAR SUDILOVSKY
• 金额: $ 10.82万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-15 至 1991-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3188940
• 关键词: autoradiography; chemical carcinogenesis; cocarcinogen; diethylnitrosamine; disease /disorder model; dosage; electron microscopy; freeze etching; gap junctions; glucose; laboratory rat; liver neoplasms; membrane lipids; membrane structure; model design /development; nitrosamines; nutrition related neoplasm /cancer; nutrition related tag; phosphatidylinositols; preneoplastic state; protein kinase C; radiotracer; sucrose; tissue /cell culture

We have recently developed a new model of hepatocarcinogenesis in the rat based on initiation by diethylnitrosamine (DEN) and promotion by high levels of sucrose. This model is of interest in studies on mechanism of promotion since, at variance with those using phenobarbital, DDT, PCBs, etc., it does not require the administration of chemicals or drugs during the promoting phase. To determine if the promotion effect of sucrose is related to the disaccharide molecule per se, the combination of glucose and fructose, or the fructose moiety alone, short-term induction- promoting experiments will be conducted. In addition, long-term experiments will be carried out to corroborate that the results of the short-term studies are definitely related to promotion activity. Since high levels of sucrose can result in increased levels of cholesterol and phospholipids, morphologic perturbations in properties of the cell membrane of hepatocytes obtained from preneoplastic nodules will be studied by the use of freeze-fracture electron microscopy. Among the membrane phospholipids whose function could change are those phosphoinositides which activate Protein Kinase C. To examine whether the complex of phosphoinositides-Proteins Kinase C is changed in enzyme-altered foci, the enzyme compartmentalization and down regulation will be studied. An effect commonly observed in promoted cells is the inhibition of intercellular communication. Its existence in high- sucrose promoted cells will be determined by freeze-fracture electron microscopy and by measuring the inhibition of metabolic cooperation in tissues cultured from preneoplastic cells. Freeze- fracture will be utilized in the study of qualitative and quantitative changes of gap-junctions. Metabolic cooperation will be analyzed by the long term and also by a recently developed technique with short term exposure time after loading the test mixture. These studies should help to clarify the nature of the promotion by sucrose and the role of the possible alterations in the membrane lipids.

我们最近开发了一种新的肝癌发生模型 在以二乙基亚硝胺(DEN)和 由高水平的蔗糖促进。此模型对以下内容感兴趣 关于促进机制的研究，与那些不同 使用苯巴比妥、滴滴涕、多氯联苯等，它不需要 推广阶段的化学品或药物管理。 以确定蔗糖的促进作用是否与 双糖分子本身，葡萄糖和葡萄糖的结合 果糖，或单独的果糖部分，短期诱导- 将进行推广试验。此外，长期的 将进行实验以证实以下结果 短期学习肯定与晋升有关 活动。因为高水平的蔗糖会导致 胆固醇和磷脂水平，形态紊乱 获得的肝细胞的细胞膜性质 用冷冻断裂法研究癌前结节 电子显微镜。在膜磷脂中，其 功能可能改变的是那些激活的肌醇磷脂 检测蛋白激酶C的复合体是否 磷脂酰肌醇-蛋白激酶C在酶改变中的变化 焦点，酶的区划和下调将 被研究。在被促进的细胞中通常观察到的一个效应是 细胞间通讯受到抑制。它的存在于高地- 用冷冻破碎法测定蔗糖促进的细胞 电子显微镜和通过测量代谢的抑制 癌前细胞培养组织中的合作。冻结- 骨折将被用于定性和定量的研究 缝隙连接的量变。新陈代谢合作将 被长期分析，也被新近开发的 加载测试后的短期曝光技术 混合物。 这些研究应该有助于澄清促销的性质 由蔗糖和可能的改变在 膜脂。