Comparative metabolism of benzo[a]pyrene and (−)benzo[a]pyrene-7,8-dihydrodiol by hepatocytes isolated from two species of bottom-dwelling fish

Abstract

In order to elucidate the biochemical bases of species differences in susceptibility to hepatotumorigenesis induced by polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BP), we investigated the metabolism of [ 3H]BP and its proximate carcinogenic metabolite (−)BP-7,8-dihydrodiol (BP-7,8-diol) by two benthic fish: brown bullheads ( Ictalurus nebulosus) (a susceptible species) and mirror carp ( Cyprinus carpio) (not known to be susceptible). Freshly isolated hepatocytes prepared from both species efficiently converted both BP and BP-7,8-diol (the proximate carcinogenic metabolite of BP) to glutathione conjugates, glucuronides and sulfates and polyhydroxylated compounds. Nevertheless, carp hepatocytes (which metabolized both BP and BP-7,8-diol about 2-fold faster than did bullhead hepatocytes) produced several-fold larger amounts of DNA adducts from both substrates, suggesting the formation by carp liver of significantly larger amounts of reactive intermediates that bind to DNA. The apparently greater susceptibility of brown bullheads to PAH-induced carcinogenesis thus awaits further clarification.