Influence of medium composition on 7-alkoxycoumarin O-dealkylase activities of rat hepatocytes in primary maintenance culture.

1. The activities of 7-methoxycoumarin (7-MCOD), 7-ethoxycoumarin (7-ECOD) and 7-propoxycoumarin (7-PCOD) O-dealkylases decreased by 75-90% during culture of rat hepatocytes for 72 h. 2. The addition of dexamethasone (D) produced a stabilization or modest enhancement of 7-ECOD and 7-PCOD activities depending on the medium used; D was without effect on 7-MCOD activity. 3. The addition of nicotinamide (N) produced some stabilization of 7-ECOD and 7-PCOD activities but not of 7-MCOD activity. 4. The addition of D + N was associated with large increases in 7-ECOD and 7-PCOD activities, again with little effect on 7-MCOD activity. 5. Ethoxyresorufin O-dealkylase activity correlated with 7-ECOD/7-PCOD activities, whereas pentoxyresorufin O-dealkylase activity correlated with 7-MCOD activity. 6. It is concluded that D exerts a selective effect on certain forms of cytochrome P-450, but that more than one mechanism is probably implicated in this effect. 7. The magnitudes of induction of 7-ECOD activity by phenobarbitone and beta-naphthoflavone were blunted when cells were treated in culture when compared to treatment in vivo; the presence of D in the culture medium did not modify this phenomenon.