Paine A J
DH Department of Toxicology, St Bartholomew's Hospital Medical College, London, U.K.
Chem Biol Interact. 1990;74(1-2):1-31. doi: 10.1016/0009-2797(90)90055-r.
Treatments affecting the loss of cytochrome P-450 in rat hepatocyte culture are reviewed and the way in which these have produced an understanding of the mechanisms involved are discussed extensively. A simple way to prevent the loss of P-450 in hepatocytes is to culture them with 0.5 mM metyrapone which appears to restore the cytochromes' synthesis and degradation to steady state values. Knowledge of this mechanism has led to the formulation of special culture medium and the application of both culture systems to the study of drug metabolism and toxicity are described. Finally the effect of these culture systems on the expression of the multiple forms of cytochrome P-450 are presented to illustrate the potential of cultured hepatocytes in induction studies.
本文综述了影响大鼠肝细胞培养中细胞色素P-450丢失的处理方法，并广泛讨论了这些方法如何增进我们对相关机制的理解。防止肝细胞中P-450丢失的一种简单方法是用0.5 mM美替拉酮培养肝细胞，美替拉酮似乎能使细胞色素的合成和降解恢复到稳态值。对这一机制的了解促使了特殊培养基的配制，并描述了这两种培养系统在药物代谢和毒性研究中的应用。最后，介绍了这些培养系统对细胞色素P-450多种形式表达的影响，以说明培养肝细胞在诱导研究中的潜力。
