Regioselective metabolism of benzo[a]pyrene and 7-chlorobenz[a]anthracene by fish liver microsomes.

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.