PATHOBIOLOGY OF HIGH DOSE SUCROSE

高剂量蔗糖的病理学

• 批准号: 3188939
• 负责人: OSCAR SUDILOVSKY
• 金额: $ 11.98万
• 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 1990-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3188939
• 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 在大鼠中，基于二乙基亚硝胺（DEN）引发， 促进高水平的蔗糖。 该模型在以下方面具有重要意义： 晋升机制的研究，因为，在不同的那些 使用苯巴比妥、滴滴涕、多氯联苯等，它不需要 在促进阶段给予化学品或药物。 为了确定蔗糖的促进作用是否与 二糖分子本身，葡萄糖和 果糖，或单独的果糖部分，短期诱导- 进行推广试验。 此外，长期 将进行实验来证实的结果 短期学习肯定与晋升有关 活动 由于高水平的蔗糖会导致 胆固醇和磷脂水平，形态学紊乱 在获得的肝细胞的细胞膜的性质中， 肿瘤前结节将通过使用冷冻骨折进行研究 电镜 在膜磷脂中， 功能可能改变的是那些激活 蛋白激酶C 为了研究是否复杂的 磷酸肌醇-蛋白激酶C在酶改变的 焦点，酶的区室化和下调将 被研究。 在促进的细胞中通常观察到的效应是 抑制细胞间通讯。 它的存在于高- 蔗糖促进的细胞将通过冷冻断裂来确定 电子显微镜检查并通过测量代谢抑制 从癌前细胞培养的组织中的合作。 别动- 骨折将用于定性和 缝隙连接的数量变化。 代谢合作将 从长远来看，也可以通过最近开发的 加载测试后短期暴露时间的技术 混合物. 这些研究应有助于澄清促销的性质 蔗糖和作用的可能改变， 膜脂