Chou M W, Miller D W, Freeman J P, Fu P P
National Center for Toxicological Research, Jefferson, Arkansas 92079.
Chem Res Toxicol. 1988 Mar-Apr;1(2):115-22. doi: 10.1021/tx00002a005.
4-(N,N-Diacetylamino)benzo[a]pyrene, a potent mutagen, is derived from a carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene. Metabolism of this compound by rat liver microsomes was studied. Metabolites were separated by reversed-phase high-performance liquid chromatography and were identified by analysis of their UV-vis absorption, mass, and proton nuclear magnetic resonance spectral data. Seven metabolites were identified, namely, the 9-phenol, 1,9-hydroquinone, and trans-9,10-dihydrodiol of 4-(N,N-diacetylamino)benzo[a]pyrene, 4-(N-acetylamino)benzo[a]pyrene, and the 5-phenol, 5,9-hydroquinone, and trans-9,10-dihydrodiol of 4-(N-acetylamino)benzo[a]pyrene. Comparison of these results with those of metabolism of benzo[a]pyrene indicates that the N,N-diacetylamino substitutent at the 4-carbon of benzo[a]pyrene inhibits metabolism at the peri position (3-carbon) and positions (6-, 7-, and 8-carbons) remote from the substituent. The results also indicate that while 4-(N,N-diacetylamino)-benzo[a]pyrene is a substrate of the rat liver microsomal deacetylase, the formed 4-(N-acetylamino)benzo[a]pyrene apparently is not a substrate.
4-（N，N-二乙酰氨基）苯并[a]芘是一种强效诱变剂，源自致癌多环芳烃苯并[a]芘。研究了该化合物在大鼠肝脏微粒体中的代谢情况。代谢产物通过反相高效液相色谱法分离，并通过对其紫外可见吸收、质谱和质子核磁共振光谱数据的分析进行鉴定。鉴定出了七种代谢产物，即4-（N，N-二乙酰氨基）苯并[a]芘的9-酚、1,9-对苯二酚和反式-9,10-二氢二醇，4-（N-乙酰氨基）苯并[a]芘，以及4-（N-乙酰氨基）苯并[a]芘的5-酚、5,9-对苯二酚和反式-9,10-二氢二醇。将这些结果与苯并[a]芘的代谢结果进行比较表明，苯并[a]芘4位的N，N-二乙酰氨基取代基抑制了周边位置（3位碳）以及远离该取代基的位置（6-、7-和8-位碳）的代谢。结果还表明，虽然4-（N，N-二乙酰氨基）苯并[a]芘是大鼠肝脏微粒体脱乙酰酶的底物，但所形成的4-（N-乙酰氨基）苯并[a]芘显然不是底物。
