RAT HEPATOCYTE CULTURES AND COCULTURES IN BIOTRANSFORMATION STUDIES OF XENOBIOTICS

Long-term cultures of hepatocytes could represent a suitable in vitro model for botransformation studies of xenobiotics. At present however, no ideal culture system can be proposed since, in all existing models , phenotypic changes occur, affecting selectively some components of p hase I and/or phase II xenobiotic metabolism. From the authors' own re sults and recent studies of several other investigators, carried out o n rat hepatocytes, it becomes clear that four groups of factors may af fect biotransformation capacity: soluble medium factors, extracellular matrix components, cell-cell interactions and factors affecting repli cation. For the maintenance of liver-specific functions, it seems of u tmost importance that the tridimensional shape of the hepatocytes is k ept. Usually, phase II enzymatic activity is better kept than that of phase I. The cytochrone P450 dependent monoxygenases, in particular, a re easily lost. Interesting is the observation that co-cultures of rat hepatocytes with rat liver epithelial cells exhibit higher and much b etter preserved phase I and phase II biotransformation than monocultur es. Clearly, further research is needed to improve this promising in v itro model.