Ueng T H, Ueng Y F, Chou M W
Institute of Toxicology, College of Medicine, National Taiwan University, Taipei.
Toxicol Lett. 1994 Jan;70(1):89-99. doi: 10.1016/0378-4274(94)90148-1.
Many polycyclic aromatic hydrocarbons (PAHs) and chlorinated PAHs in the environment are potent mutagens and carcinogens. Using benzo[a]pyrene (BaP) and 7-chlorobenz[a]anthracene (7-Cl-BA) as representatives of PAHs and chlorinated PAHs, respectively, we studied the metabolism of these compounds in liver microsomes of Tilapia (Oreochromis hybrid), one of the most common fish in south Asia. The regioselective metabolism of BaP and 7-Cl-BA by the fish liver microsomes resulted in the formation of hydroxylated and trans-dihydrodiol metabolites of both BaP and 7-Cl-BA. The metabolites were purified by HPLC and identified by both UV/VIS and mass spectroscopic methods. The fish liver microsomes metabolized BaP to form BaP-7,8-dihydrodiol (11%), 3-hydroxy-BaP (17%), and 9-hydroxy-BaP (22%) as the major products and metabolized 7-Cl-BA to form 7-Cl-BA trans-8,9-dihydrodiol as the major metabolite (40%). The Tilapia liver microsomal P-450 enzyme activities were inducible by pretreatment with 3-methylcholanthrene (3-MC), which increased microsomal aryl hydrocarbon hydroxylase and 7-ethoxyresorufin O-deethylase activities by 74- and 360-fold, respectively. The induction of these enzymes by 3-MC was greater in fish microsomes than in rat liver. This study is the first to demonstrate the regioselective metabolism of BaP and 7-Cl-BA by fish liver microsomes.
环境中的许多多环芳烃（PAHs）和氯化多环芳烃都是强效诱变剂和致癌物。我们分别以苯并[a]芘（BaP）和7-氯苯并[a]蒽（7-Cl-BA）作为多环芳烃和氯化多环芳烃的代表，研究了这些化合物在南亚最常见的鱼类之一罗非鱼（奥利亚罗非鱼）肝脏微粒体中的代谢情况。罗非鱼肝脏微粒体对BaP和7-Cl-BA的区域选择性代谢导致形成了BaP和7-Cl-BA的羟基化和反式二氢二醇代谢产物。这些代谢产物通过高效液相色谱法（HPLC）进行纯化，并通过紫外/可见光谱法和质谱法进行鉴定。罗非鱼肝脏微粒体将BaP代谢形成BaP-7,8-二氢二醇（11%）、3-羟基-BaP（17%）和9-羟基-BaP（22%）作为主要产物，并将7-Cl-BA代谢形成7-Cl-BA反式-8,9-二氢二醇作为主要代谢产物（40%）。用3-甲基胆蒽（3-MC）预处理可诱导罗非鱼肝脏微粒体中的P-450酶活性，这分别使微粒体芳烃羟化酶和7-乙氧基试卤灵O-脱乙基酶活性提高了74倍和360倍。3-MC对这些酶的诱导在鱼类微粒体中比在大鼠肝脏中更强。本研究首次证明了鱼类肝脏微粒体对BaP和7-Cl-BA的区域选择性代谢。
