Induction of cytochrome P450 1A in the American Eel by model halogenated and non-halogenated aryl hydrocarbon receptor agonists.
Eels (Anguilla sp.) have phylogenetic, life history, and morphological characteristics which distinguish them from many other species that have been examined for cytochrome P450 1A (CYP1A) induction. Members of the family Anguillidae often occur in regions of the coastal environment that are heavily impacted by chemical contamination. Although eels have been suggested to be a useful species for biomonitoring, the sensitivity with which eel CYP1A is induced by aryl hydrocarbon receptor (AHR) agonists is not known. We investigated the dose-dependent induction of hepatic CYP1A in the American eel (Anguilla rostrata). Eels from an uncontaminated site were injected intra-peritoneally with the model AHR agonists ß-naphthoflavone (BNF), benzo[a]pyrene (B[a]P) or 3,3',4,4-tetrachlorobiphenyl (TCB) at increasing doses (BNF at 0.1, 1, 10 and 100 mg/kg, B[a]P at 0.1, 1 and 10 mg/kg, and TCB at 0.1, 1, 10 and 20 mg/kg). All three compounds produced dose-dependent induction of CYP1A content and catalytic activity. An estimated ED(50) for induction of liver microsomal EROD activity by TCB was approximately 5 mg/kg, indicating only moderate sensitivity. At comparable doses of 1 and 10 mg/kg (or 3-4 and 30-40 µmol/kg), BNF and B[a]P had 2-3-fold greater effect than TCB in eliciting hepatic CYP1A induction. Injection of radiolabeled B[a]P and TCB resulted in similar dose-dependent concentrations of these compounds in eel liver, and the hepatic inducer concentrations and CYP1A levels were correlated positively. Eels collected from New Bedford Harbor (NBH), a Superfund site highly contaminated by polycyclic aromatic hydrocarbons and polychlorinated biphenyls, had levels of microsomal CYP1A protein and EROD activity that were equivalent to the highest levels induced experimentally. Eels from less contaminated sites had correspondingly less CYP1A expression. The responses to B[a]P or BNF as compared to TCB suggest a lower efficacy and/or potency for CYP1A induction by TCB which could involve differences in the mechanisms of responses to these compounds in eels. However, the moderate sensitivity and the CYP1A induction in NBH eels support suggestions that eels may be useful in monitoring more contaminated regions.
Schlezinger
JJ
Biology Department, Woods Hole Oceanographic Institution, Redfield 342, MS 32, 02543, Woods Hole, MA, USA
Stegeman
JJ