CYTOCHEMICAL STUDIES IN TOXIC LIVER INJURY

肝脏对损伤的反应包括退化和修复。 流程。事实上，前者是后者的倡导者。两种语言的分离 两个是必要的，以试图定义所涉及的机制改变 在损伤和细胞死亡中的调节。几种卤代有机物，包括 CCl4，造成肝脏损伤和死亡。目前的证据并不表明 针对所有这些不同代理的简单目标系统，事实上， 对几种制剂的结构、功能和时间反应 有所不同。CCl4在内质网中的产生和早期变化 在质膜中，在完整的动物身上观察到 可以证明细胞死亡。我们建议继续探讨 细胞膜麦角质的变化以确定化学物质 发生的变化，并将它们与CCl14的新陈代谢联系起来。通过 批判性地关注互动出现的时间，他们的作用 细胞的生物学改变可以被描述。比较研究使用 整个动物、分离的灌流肝脏和培养中的肝细胞将 提供了一种分析这些变化的生物学特性的方法。此外，一个 全肝高能的临界相关时程研究 随后将进行核磁共振研究，包括磷酸键和二价金属离子助熔剂。 这些数据应该能进一步洞察细胞对 有机氯化合物及其参与细胞损伤的机制。

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.