Long-term immune dysfunction in rainbow trout (Oncorhynchus mykiss) exposed as embryos to aflatoxin B sub(1)

The mycotoxin, aflatoxin B sub(1) (AFB sub(1)), is a polycyclic aromatic hydrocarbon (PAH) that is associated with hepatic carcinogenesis and immunomodulation in a broad spectrum of vertebrates. In rainbow trout, the transformation of AFB sub(1) to a biologically active form occurs via pathways similar to those in mammals. AFB sub(1) is transformed to AFB sub(1)-8,9,-epoxide by enzymes of the cytochrome P450 family. This epoxide covalently binds to DNA to form 8,9-dihydro-8-(N super(7)-guany)-9-hydroxyaflatoxin B sub(1). Up-regulation of cytochrome P450 mRNA synthesis occurs following aflatoxin binding to the aromatic hydrocarbon receptor and subsequent signal transduction. Aflatoxin B sub(1) has been found to be a potent immunomodulator in endotherms. Exposure to AFB sub(1) results in the reduction of cytokine, macrophage function and lymphocyte activity. Trout exposed to very low concentrations of AFB sub(1) in feed or exposed as embryos have a very high incidence of carcinogenesis. The use of the trout/AFB sub(1) model for the study of PAH-induced immunomodulation in ectotherms is based on the known sensitivity of the fish to this carcinogen and also on the large body of data available on the immunomodulatory effects of AFB sub(1) in endotherms that serves as a source for comparison. In this study the mitogen responses of normal rainbow trout are compared to those of trout exposed as embryos to AFB sub(1). This resulted in long-term alterations in mitogenesis and immunoglobulin production and is characterised by differential leucocyte sensitivity.