The Japanese medaka (Oryzias latipes) model: applicability for investigating the immunosuppressive effects of the aquatic pollutant benzo[a]pyrene (BaP)

Abstract

Despite the fact that BaP is a carcinogen, mammalian immunosuppressant, and ubiquitous aquatic pollutant, knowledge regarding the effects of BaP on the immune system of fish is still lacking. To begin to fill this gap, studies were conducted in medaka to examine the effects and mechanisms by which BaP exposure might alter host immunocompetence. Fish, exposed by IP injection of BaP (2–600 μg/g BW), were examined after 48 h for effects upon immune function and CYP1A expression/activity. Benzo[a]pyrene, at a concentration below that which increased levels of CYP1A expression/activity (2 μg BaP/g BW) suppressed lymphocyte proliferation. Concentrations of BaP at 20 and 200 μg/g BW, suppressed antibody-forming cell (AFC) numbers, superoxide production, and host resistance against bacteria. In contrast, exposure to the low affinity aryl hydrocarbon receptor (AhR) agonist, benzo[e]pyrene (BeP), neither induced CYP1A expression nor altered immune function. Given the lack of immunosuppressive effects produced by BeP, and the fact that exposure to the AhR antagonist (and CYP1A inhibitor) α-naphthoflavone (ANF) ameliorated the suppressive effects of BaP upon AFC numbers, the AhR pathway (including CYP1A-mediated production of reactive BaP metabolites) appears important in mediating BaP-induced immunotoxicity in fish, as in mammals. In the past, the medaka has proven a successful model for assessing carcinogenic agents. These studies have demonstrated its utility for also determining the immunosuppressive effects of an important aquatic contaminant.