Induction of drug metabolism. 3. Further information of a new P-450 hemoprotein after treatment of rats with 3-methylcholanthrene.

Drugs have been classified into two groups depending upon whether they form type I or type II difference spectra when they combine with microsomal hemoprotein. Using hexobarbital and aniline as representatives of type I and type II drugs, respectively, the effect that time administration of phenobarbital or 3-methylcholanthrene might have on the binding of microsomal hemoprotein to these drugs was studied. Phenobarbital produced marked increases in type I and type II binding, but 3-methylcholanthrene caused an increase in type II binding only. These changes in the binding properties were reflected in the oxidation of hexobarbital and aniline; as the administration of 3-methylcholanthrene to rats was continued for 5 days, the microsomes from these animals increased their ability to oxidize aniline, but gradually lost their ability to oxidize hexobarbital. The type II binding site was much more stable to digestion with steapsin and to storage in the cold. Thus steapsin or cold storage produced much the same effect on the binding properties of microsomal hemoprotein as did the administration of 3-methylcholanthrene. These studies support the previous conclusion that the administration of 3-methylcholanthrene causes the formation of a new microsomal hemoprotein (cytochrome P1-450).