Responsiveness of Carmustine (BCNU) treated mice to induction and inhibition of mixed function oxygenases

The responsiveness of BCNU treated mice to phenobarbital (Pb) induction of hepatic microsomal mixed function oxygenase (MFO) activity was studied. BCNU (30 mg/kg ip) produced significant (P less than 0.05) decreases in cytochrome P-450, total ethylmorphine metabolism (TEM) and ethylmorphine N-demethylase (EMN) by 21 days after treatment. The specific activities of TEM and EMN were decreased more than was P-450 content. Benzpyrene hydroxylase (BPH) was increased and 7-ethoxycoumarin 0-deethylase (ECD) was unaffected at this time. Pb induction beginning on day 17 after BCNU treatment resulted in a greater inductive response in the BCNU treated mice than in controls. The specific activities of all MFO enzymes studied were more markedly affected than were the raw activities suggesting activation. However, the responsiveness of the MFOs to the actions of inhibitory was not markedly influenced by BCNU pretreatment.