Substrate Specificity of Rabbit Liver Monooxygenase Induced by PCBs

Exposure of rats to PCBs induces the two groups of hepatic monooxygenases that are inducible by phenobarbital (PB) or methylcholanthrene (MC)(Alvares et al., PNAS 70, 1321, 1973). By contrast, in rabbit liver a number of monooxygenase activities which are enhanced by PB neither respond to the application of PCBs nor to MC (Wolff et al., Biochem.Pharmac. 26, 783, 1977). This suggests that in rabbit liver the PCB-inducible monooxygenase might be of the cytochrome P-448 form. To verify this assumption, 3 reactions were studied which are stimulated by MC treatment. Rabbits were treated with a single oral dose of 50 mg/kg PCB (CLOPHEN A 50) on 5 consecutive days. Liver microsomes were isolated 3 days thereafter. PCB treatment enhanced N-hydroxylation of acetylaminofluorene (AAF) 8-fold, and acetanilide and zoxazolamine hydroxylation almost 3-fold. A 4-fold increase of AAF and a 2-fold increase of acetanilide and zoxazolamine metabolism was observed after MC treatment (2 × 20 mg/kg) indicating a close relationship between PCB and MC mediated induction.