Differentiation of cytochrome P-450 inducers on the basis of 7-alkoxycoumarin O-dealkylase activities

Abstract

1. The high-affinity and total activities of 7-methoxycoumarin O-demethylase and of 7-ethoxycoumarin O-deethylase were measured in liver microsomes isolated from rats treated with prototypic inducers belonging to the main classes of microsomal enzyme inducers currently recognized.

2. Each inducer (with the exception of clofibrate which was ineffective) produced a unique induction profile, indicating the possibility of using these two enzymes, each measured at two substrate concentrations, for characterization of the inducing potential of novel xenobiotics.

3. Differences between p,p'-DDT and phenobarbitone in the induction profiles indicate that DDT may not be a pure ‘phenobarbitone-type’ inducer as has been proposed hitherto.