Gray J E
Environ Health Perspect. 1976 Jun;15:47-54. doi: 10.1289/ehp.761547.
Philosophic concepts and pragmatic approaches toward improved understanding of the effect of drugs in the hepatocyte are reviewed. No set pattern of studies is advocated but rather observations are encouraged within the framework of studies that provide for varied exposure of the hepatocyte. Clinical usage should be imitated to provide earliest possible indications of toxicity in man. The need for definitive characterization through utilization of appropriate methodology derived from cross-fertilization of related disciplines is stressed. Both minimal and maximal dose effects should be established. Selected use of electron microscopy has become essential for characterizing responses of the liver to injury. The advantages of the toluidine blue-stained Epon "thick" sections are emphasized. Such observations are used to implement the utility of serial biopsies from the beagle dog prior to and during long-term study of potential hepatic injury. Examples of the critical effects of drug concentration within the hepatocyte are presented.
本文综述了关于更好地理解药物对肝细胞作用的哲学概念和实用方法。文中不提倡固定的研究模式，而是鼓励在能使肝细胞有不同暴露情况的研究框架内进行观察。应效仿临床用药方式，以便尽早发现人体中的毒性迹象。强调了利用相关学科交叉融合产生的适当方法进行明确表征的必要性。应确定最小和最大剂量效应。选择使用电子显微镜对于表征肝脏对损伤的反应已变得至关重要。文中强调了甲苯胺蓝染色的环氧树脂“厚”切片的优势。这些观察结果被用于在对潜在肝损伤进行长期研究之前和期间，实施从比格犬身上进行系列活检的效用。文中还列举了肝细胞内药物浓度的关键作用实例。
