Regioselective and Stereoselective Metabolism of Benzo[a]pyrene and 7-Chlorobenz[a]anthracene by Fish Liver Microsomes

Abstract

Many polycyclic aromatic hydrocarbons (PAH) and chlorinated PAH, such as benzo[a]pyrene (BaP) and 7-chlorobenz[a]anthracene (7-Cl-BA) are potent environmental pollutants which may contaminate surface waters and poison aquatic species. Since BaP is a hepatocarcinogen to rainbow trout, the in vitro metabolism of BaP and 7-Cl-BA mediated by liver microsomes of Tilapia, one of the most common fish species in south Asia, was chosen to study. Pretreatment with 3-methylcholanthrene increased activities of fish liver microsomal aryl hydrocarbon hydroxylase, and 7-ethoxyresorufin O-deethylase by 74- and 360-fold more than the uninduced microsomal enzymes, respectively. The regioselective metabolism of BaP by the fish liver microsomes resulted in the formation of BaP-t-7,8-diol as a major metabolite. However, the metabolism of 7-Cl-BA by fish microsomes resulted in the formation of phenolic metabolites of 7-Cl-BA and 7-Cl-BA-t-8,9-diol as the major metabolites, which may indicate a detoxification pathway. Tilapia liver microsomes exhibited stereoselectivity toward the formation of dihydrodiols of BaP and 7-Cl-BA as shown by their circular dichroism spectra. The study of the regio- and stereo-selective metabolism of BaP and 7-Cl-BA by fish liver microsomes is important to the mechanistic study on the risk assessment of fish exposed to a polluted environment and subsequently to human health.

Key Words:

• Benzo[a]pyrene (BaP)
• 7-chlorobenz[a]anthracene (7-Cl-BA)
• metabolism
• fish microsomes
• regioselectivity
• stereoselectivity.