The maintenance of cytochrome P-450 in rat hepatocyte culture: some applications of liver cell cultures to the study of drug metabolism, toxicity and the induction of the P-450 system.
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.
Paine
A J
AJ
DH Department of Toxicology, St Bartholomew's Hospital Medical College, London, U.K.
D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D010600:Pharmacology; D051381:Rats
D004364:Pharmaceutical Preparations; D003577:Cytochrome P-450 Enzyme System