Altered CYP1A expression in Fundulus heteroclitus adults and larvae: a sign of pollutant resistance?

Abstract

This study addresses the development of resistance to CYP1A induction in a population of Fundulus heteroclitus from highly contaminated Newark Bay, NJ. CYP1A is a P450 monooxygenase whose expression is induced in vertebrates by numerous organic contaminants, including polychlorinated biphenyls (PCBs). Reduced expression of CYP1A in highly contaminated populations may represent resistance to chemical stressors. Adult F. heteroclitus from Newark Bay and a reference site were held in clean seawater for 6 months to allow them to depurate their contaminant body burdens. These fish were then exposed to a single intraperitoneal injection of PCBs during gametogenesis and CYP1A expression measured in parents and larvae. Hatching success, larval survival and larval growth were also measured; no effect of PCB treatment was observed in these parameters. Fish from the reference population exhibited a strong CYP1A dose-response to PCB treatments. Reference adult males treated with 0, 10 or 100 mg PCB (kg body weight) −1 had hepatic ethoxyresorufin O-deethylase (EROD) activities of 132±46.1, 43.3±59.5 and 345.4±197.5 pmol min −1 mg −1, respectively, and CYP1A protein levels of 7±5.6; 6.1±4.8 and 92.6±25 pmol mg −1 (means±SD) at 7 weeks post-injection. CYP1A expression in 24-h and 8-day post-hatch larvae from PCB-treated reference parents was measured immunohistochemically and revealed a strong and persistent induction that was dose-related. Further, larval organs responded sequentially to increasing parental PCB dose in the following order: hepatocytes, gill, gut and heart; the kidney appeared to express CYP1A constituitively. In contrast to the reference fish, Newark Bay adults and larvae failed to show induction of CYP1A in response to any PCB treatment. These results indicate that the Newark Bay population has acquired an altered response to CYP1A inducers that is both persistent and possibly heritable, that use of CYP1A as a biomarker may be misleading under conditions of chronic or extreme exposure, and emphasize the need for carefully designed studies which employ indicators in addition to CYP1A as biomarkers of exposure or effects.