Comparative metabolism of phenanthrene and benzo[f]quinoline by rat liver microsomes

The metabolism of benzo[f]quinoline (BfQ) and its carbon analog phenanthrene has been compared in incubations with liver microsomes from control, 3-methylcholanthrene (3-MC)- and phenobarbital (PB)-pretreated rats. The rates of phenanthrene metabolism by the three types of microsomes were 0.7, 4.1 and 1.5 nmol/mg protein per min, respectively; the values for BfQ were 0.5, 3.7 and 2.5, respectively. Besides N-oxidation, the metabolism of BfQ by all the above microsomes was almost exclusively at the benzo-ring (49-69%) while that of phenanthrene was predominantly at the K-region (50-71%). Phenanthrene-1,2-dihydrodiol, a precursor of the bay-region diol epoxide of phenanthrene, was produced many times more than phenanthrene-3,4-dihydrodiol by both 3-MC- and PB-induced microsomes. While BfQ-7,8-dihydrodiol, the precursor of the bay-region diol epoxide of BfQ, was the predominant metabolite with 3-MC-induced microsomes, it was a minor metabolite with PB-induced microsomes. The benzo-ring oxidation of BfQ, but not of phenanthrene, was position-specific, i.e. predominantly 7,8-oxidation by 3-MC-induced microsomes and 9,10-oxidation by PB-induced microsomes, and implies that azasubstitution results in a site-specific attack by different cytochromes P-450.