Kandaswami C, Kumar S, Rutkowski J P, Sikka H C
Great Lakes Laboratory, State University of New York College, Buffalo 14222.
Cancer Lett. 1988 Dec 15;43(3):197-205. doi: 10.1016/0304-3835(88)90171-1.
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 aza-substitution results in a site-specific attack by different cytochromes P-450.
在与来自对照、经3-甲基胆蒽（3-MC）和苯巴比妥（PB）预处理大鼠的肝微粒体进行的孵育实验中，对苯并[f]喹啉（BfQ）及其碳类似物菲的代谢情况进行了比较。三种类型微粒体对菲的代谢速率分别为每分钟0.7、4.1和1.5 nmol/mg蛋白质；BfQ的代谢速率值分别为0.5、3.7和2.5。除了N-氧化外，上述所有微粒体对BfQ的代谢几乎都仅发生在苯环上（49 - 69%），而菲的代谢主要发生在K区域（50 - 71%）。3-MC和PB诱导的微粒体产生的菲-1,2-二氢二醇（菲的湾区二醇环氧化物的前体）比菲-3,4-二氢二醇多很多倍。虽然BfQ-7,8-二氢二醇（BfQ的湾区二醇环氧化物的前体）是3-MC诱导微粒体的主要代谢产物，但它是PB诱导微粒体的次要代谢产物。BfQ的苯环氧化具有位置特异性，而菲没有，即3-MC诱导的微粒体主要进行7,8-氧化，PB诱导的微粒体主要进行9,10-氧化，这表明氮杂取代导致不同细胞色素P-450进行位点特异性攻击。
