CYTOCHEMICAL STUDIES IN TOXIC LIVER INJURY

肝脏对损伤的反应涉及退行性和修复性 流程. 事实上，前者引发了后者。 的分离 第二，有必要尝试定义改变的机制。 调节损伤和细胞死亡。 几种卤代有机物，包括 CCl4，产生肝损伤和死亡。 目前的证据并不表明 简单的目标系统，为所有这些不同的代理，事实上， 对几种药物的结构、功能和时间反应 不同。 CCl4的产生和内质网的早期改变 在完整动物中观察到， 可以证明细胞死亡。 我们建议继续探讨 改变细胞膜的内质网，以确定化学 发生的变化，并将它们与CCl14的代谢联系起来。 通过 关键注意互动的出现时间，他们的作用， 可以描述细胞的改变的生物学。 比较研究使用 整个动物、离体灌注的肝脏和培养的肝细胞将 提供了一种分析这些变化的生物学的方法。 此外，A 全肝高能临界相关时程研究 磷酸键和二价金属离子通量将通过NMR跟踪。 这些数据应该提供进一步了解细胞反应， 有机氯化合物和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.