In Vitro Induction of Ethoxyresorufin-o-deethylase and Porphyrins by Halogenated Aromatic Hydrocarbons in Avian Primary Hepatocytes

Ethoxyresorufin-O-deethylase (EROD) and porphyrin induction responses of primary hepatocytes to halogenated aromatic hydrocarbons (HAHs) were examined in newly hatched domestic chickens, herring gulls, ring-billed gulls, double-crested cormorants, and Forster’s terns. Concentration–response relationships were determined for both biochemical responses in hepatocyte preparations derived from individual avian livers (except for the tern). The choice of vehicle used to dose chicken hepatocytes greatly affected the potencies and efficacies of HAHs. Dimethyl sulfoxide resulted in median effective concentration (EC50) values for EROD induction that were between 10 and 15 times less than isooctane (isooctane was used throughout the study). Neither vehicle induced EROD activity by itself. Concentration-dependent increases in EROD activity were observed with several HAHs, and their potencies (EC50 values) were compared to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within each hepatocyte preparation to determine relative potency factors (RPFs). Differences in sensitivity to these responses were observed among individuals within each of the species and among species. Median EC50 values (nM) for EROD induction by TCDD were 0.72, 13, 20, 25, and 150 for the chicken, cormorant, ring-billed gull, herring gull, and tern hatchling, respectively. Relative potency factors for several HAHs were different, in both ranking and potency, from those generally derived in mammalian hepatocytes. Porphyrin accumulation was observed occasionally with the most potent aryl hydrocarbon receptor agonists, but most HAHs were not tested at concentrations sufficiently high to observe a consistent response. This study provides information on interindividual and interspecies differences in responsiveness to TCDD-like compounds and provides species-specific RPFs that may prove useful for the purpose of hazard and risk assessment for fish-eating birds. Keywords—Avian hepatocytes Ethoxyresorufin O-deethylase Halogenated aromatic hydrocarbons Porphyrins 2,3,7,8-Tetrachlorodibenzo-p-dioxin