Mushtaq M, Weems H B, Yang S K
Arch Biochem Biophys. 1986 Apr;246(1):478-87. doi: 10.1016/0003-9861(86)90494-7.
The non-K-region benz[a]anthracene (BA) 8,9- and 10,11-epoxides were isolated by normal-phase high-performance liquid chromatography as rat liver microsomal metabolites of BA. The identities of these epoxides were established by ultraviolet and mass spectral analyses and were further validated by the microsomal epoxide hydrolase catalyzed conversion to BA trans-8,9-dihydrodiol and trans-10,11-dihydrodiol, respectively. Circular dichroism spectral analyses of the metabolically formed non-K-region epoxides and dihydrodiols and mass spectral analyses of metabolically formed 18O-labeled non-K-region dihydrodiols and their acid-catalyzed dehydration products indicated that BA (8R,9S)-epoxide and (10S,11R)-epoxide were the predominant enantiomers formed in the metabolism at the 8,9- and 10,11- aromatic double bonds of BA, respectively, by rat liver microsomes. This is the first example demonstrating the direct detection and stereoselective metabolic formation of non-K-region epoxides of a polycyclic aromatic hydrocarbon.
通过正相高效液相色谱法分离得到了非K区域苯并[a]蒽（BA）的8,9 - 环氧化物和10,11 - 环氧化物，它们是BA在大鼠肝脏微粒体中的代谢产物。通过紫外光谱和质谱分析确定了这些环氧化物的结构，并分别通过微粒体环氧化物水解酶催化转化为BA反式-8,9 - 二氢二醇和反式-10,11 - 二氢二醇进一步验证。对代谢生成的非K区域环氧化物和二氢二醇进行圆二色光谱分析，以及对代谢生成的18O标记的非K区域二氢二醇及其酸催化脱水产物进行质谱分析，结果表明，BA（8R,9S）-环氧化物和（10S,11R）-环氧化物分别是大鼠肝脏微粒体在BA的8,9 - 和10,11 - 芳香双键代谢过程中形成的主要对映体。这是首次证明直接检测多环芳烃非K区域环氧化物及其立体选择性代谢形成的实例。
