Holder G, Yagi H, Dansette P, Jerina D M, Levin W, Lu A Y, Conney A H
Proc Natl Acad Sci U S A. 1974 Nov;71(11):4356-60. doi: 10.1073/pnas.71.11.4356.
The mobilities of 24 potential metabolites of benzo[a]pyrene were examined with high pressure liquid chromatography. Twelve phenols, five quinones, four dihydrodiols, and three oxides were studied. The chromatographic procedure employed allowed the separation and quantitation of benzopyrene metabolites into three major groups consisting of phenols, quinones, and dihydrodiols. Two of the benzopyrene oxides were unstable during chromatography, whereas the third oxide was more stable and chromatographed in the quinone fraction. Treatment of rats with phenobarbital or 3-methylcholanthrene enhanced the metabolism of benzopyrene by liver microsomes and altered the relative amounts of the various metabolites formed. In the absence of epoxide hydrase (EC 4.2.1.63), benzopyrene was metabolized primarily to phenols and quinones but was not appreciably metabolized to dihydrodiols by a solubilized, reconstituted cytochrome P-448 monooxygenase system. Addition of partially purified epoxide hydrase resulted in the formation of benzopyrene dihydrodiols with a concomitant decrease in the formation of phenolic metabolites, indicating that benzopyrene undergoes metabolism via arene oxides that are precursors for dihydrodiols and phenols.
用高压液相色谱法检测了苯并[a]芘24种潜在代谢物的迁移率。研究了12种酚类、5种醌类、4种二氢二醇类和3种氧化物。所采用的色谱方法可将苯并芘代谢物分离并定量为酚类、醌类和二氢二醇类三大主要类别。其中两种苯并芘氧化物在色谱过程中不稳定,而第三种氧化物更稳定,在醌类组分中进行色谱分析。用苯巴比妥或3-甲基胆蒽处理大鼠可增强肝微粒体对苯并芘的代谢,并改变所形成的各种代谢物的相对量。在缺乏环氧化物水解酶(EC 4.2.1.63)的情况下,苯并芘主要代谢为酚类和醌类,但通过溶解的、重组的细胞色素P-448单加氧酶系统不会明显代谢为二氢二醇类。添加部分纯化的环氧化物水解酶会导致苯并芘二氢二醇类的形成,同时酚类代谢物的形成减少,这表明苯并芘通过作为二氢二醇类和酚类前体的芳烃氧化物进行代谢。