EXPRESSION AND INDUCTION OF DRUG-METABOLIZING-ENZYMES IN CULTURED FETAL-RAT HEPATOCYTES

An in vitro experimental model, fetal rat hepatocytes in culture, was metabolically characterized. Several enzymatic activities were express ed in these hepatocytes, namely, testosterone hydroxylations. Hepatocy tes cultured up to 3 weeks in the presence of dexamethasone and phenob arbital still expressed some drug-metabolizing enzyme activities (e.g. , ECOD). The enzymatic activities were measured both directly on monol ayers during culture and on the corresponding harvested and homogenize d cells. The results correlate perfectly with each other. The 'on cell ' procedure allows us to repeat the assay or to measure several activi ties on the same cells at different time intervals. The presence of de xamethasone in the culture medium allows the expression and the induct ion of several cytochrome P450 isoenzymes, namely, those hydroxylating testosterone. This makes the model particularly attractive for induct ion experiments as well as for metabolic or toxicological studies need ing longer treatments.