CYTOCHEMICAL STUDIES IN TOXIC LIVER INJURY

中毒性肝损伤的细胞化学研究

• 批准号: 3226559
• 负责人: JOHN R MACDONALD
• 金额: $ 15.51万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1987-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3226559
• 关键词: affinity chromatography; carbon tetrachloride poisoning; cell death; cell free system; cell membrane; cellular pathology; cytochrome P450; cytotoxicity; electron microscopy; endoplasmic reticulum; freeze etching; gas chromatography; gel electrophoresis; gel filtration chromatography; halocarbon compound; hepatotoxin; histochemistry /cytochemistry; immunoelectrophoresis; ion transport; liver regeneration; liver toxic disorder; membrane structure; messenger RNA; nitrosamines; nuclear magnetic resonance spectroscopy; nucleic acid metabolism; peroxidation; phosphorylation; radiotracer; thin layer chromatography; tissue /cell culture; toxin metabolism; unspecific monooxygenase

The response of the liver to injury involves degenerative and reparative processes. In fact, the former initiate the latter. The separation of the two is necessary to attempt to define the mechanism involved in altered regulation in injury and in cell death. Several haloorganics, including CCl4, produce liver injury and death. Current evidence does not suggest simple target systems for all these diverse agents and, in fact, the structural and functional and temporal response to the several agents differs. CCl4 produces and early alteration in the endoplasmic reticulum and in the plasma membrane, observed in intact animals before the time when cell death can be demonstrated. We propose to continue to explore the alterations in the ergastoplasm of cell membranes to define the chemical changes that occur, and to relate them to the metabolism of CCl14. By critical attention to time of appearance of interaction, their role the altered biology of the cell may be described. Comparative studies using whole animals, isolated perfused livers, and hepatocytes in culture will provide a means of assaying the biology of these changes. Additionally, a critical correlative time course study of the whole liver high energy phosphate bonds and divalent metal ion fluxes will be followed by NMR. These data should provide further insight into cell responses to organochlorine compounds and the mechanisms involved in cell injury.

肝脏对损伤的反应包括退行性和修复性