Comparativein Vitroandin VivoBenzo[a]pyrene–DNA Adduct Formation and Its Relationship to CYP1A Activity in Two Species of Ictalurid Catfish☆

We have measured the formation and persistence ofbenzo[a]pyrene (BaP)–DNA adducts in the liver oftwo closely related species of fish, the brown bullhead(Ameriurus nebulosus) and the channel catfish(Ictalurus punctatus) using the32P-postlabeling method. Liver microsomalethoxyresorufin-O-deethylase (EROD) activity,arylhydrocarbon hydroxylase (AHH) activity, andin vitromicrosome-mediated DNA binding were all significantly higher in thechannel catfish. In anin vivotime-course experiment, fishwere either induced with βNF followed by a single BaP ip injection(20 mg/kg) or treated with corn oil. BaP–DNA adducts and EROD activityin liver were analyzed 1, 3, 7, 14, and 45 days after the BaP dosage.As in thein vitroexperiments, EROD activities in channelcatfish were significantly higher at most time points than in bullheadliver (p< 0.05). However, in contrast tothein vitrodata, the BaP–DNA adduct profile revealedsignificantly higher levels of adducts in the bullhead than the channelcatfish throughout the time course (p<0.05). Prior induction with βNF did not significantly affect thelevel or type of adduct binding to DNA in either species. Furthercharacterization of the major adduct by HPLC confirmed it to be theanti-BPDE-dGuo adduct. Analysis of tissue distribution of[14C]BaP in the two species suggested similar absorptionand initial distribution, but slower elimination from the liver ofbullhead than the catfish. The BaP–adduct profiles were consistentwith the relative species susceptibility to polycyclic aromatichydrocarbon-induced liver neoplasia. EROD activities, however, werenegatively associated with adduct levels followingin vivoexposure.