Effects of ethanol and clofibrate on expression of cytochrome P-450 enzymes and epoxide hydrolase in cultures and cocultures of rat hepatocytes

Eur J Biochem. 1991 Aug 15;200(1):255-61. doi: 10.1111/j.1432-1033.1991.tb21074.x.


Cultured and cocultured rat hepatocytes were used to study the effects of ethanol and clofibrate on cytochrome P-450 (P-450) enzymes and epoxide hydrolase. We showed that in the presence of ethanol, clofibrate or both compounds, rat hepatocytes were able to express, after 3 days of pure culture, quantitatively and qualitatively reasonable levels of most cytochrome P-450 enzymes and epoxide hydrolase, compared to freshly isolated hepatocytes. However, ethanol induced the P-450IA subfamily, and clofibrate the P-450-IVA subfamily. In cocultures, after 6 days, most P-450 enzymes were still expressed while P-450IIC11 was completely lost. Ethanol and clofibrate had the same effect as in pure culture. These results show, by modifying culture medium conditions and cell-cell interactions, that it is possible to maintain reasonable xenobiotic-metabolizing-enzyme expression; however, these conditions have to be improved in order to preserve better P-450 expression. The mechanism of these effects and the inducibility of these systems remain to be elucidated by a study at molecular level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Clofibrate / pharmacology*
  • Culture Media
  • Culture Techniques
  • Cytochrome P-450 Enzyme System / metabolism*
  • Epoxide Hydrolases / metabolism*
  • Ethanol / pharmacology*
  • Immunoblotting
  • Liver / cytology
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Rats
  • Rats, Inbred Strains


  • Culture Media
  • Ethanol
  • Cytochrome P-450 Enzyme System
  • Epoxide Hydrolases
  • Clofibrate