COMPARATIVE IN-VITRO AND IN-VIVO BENZO[A]PYRENE-DNA ADDUCT FORMATION AND ITS RELATIONSHIP TO CYP1A ACTIVITY IN 2 SPECIES OF ICTALURID CATFISH

We have measured the formation and persistence of benzo[a]pyrene (BaP) -DNA adducts in the liver of two closely related species of fish, the brown bullhead (Ameriurus nebulosus) and the channel catfish (Ictaluru s punctatus) using the P-32-postlabeling method. Liver microsomal etho xyresorufin-O-deethylase (EROD) activity, arylhydrocarbon hydroxylase (AHH) activity, and in vitro microsome-mediated DNA binding were all s ignificantly higher in the channel catfish. In an in vivo time-course experiment, fish were either induced with beta NF followed by a single BaP ip injection (20 mg/kg) or treated with corn oil. BaP-DNA adducts and EROD activity in liver were analyzed 1, 3, 7, 14, and 45 days aft er the BaP dosage. As in the in vitro experiments, EROD activities in channel catfish were significantly higher at most time points than in bullhead liver (p < 0.05). However, in contrast to the in vitro data, the BaP-DNA adduct profile revealed significantly higher levels of add ucts in the bullhead than the channel catfish throughout the time cour se (p < 0.05). Prior induction with beta NF did not significantly affe ct the level or type of adduct binding to DNA in either species. Furth er characterization of the major adduct by HPLC confirmed it to be the anti-BPDE-dGuo adduct. Analysis of tissue distribution of [C-14]BaP i n the two species suggested similar absorption and initial distributio n, but slower elimination from the liver of bullhead than the catfish. The BaP-adduct profiles were consistent with the relative species sus ceptibility to polycyclic aromatic hydrocarbon-induced liver neoplasia . EROD activities, however, were negatively associated with adduct lev els following in vivo exposure. (C) 1998 Academic Press.