Interaction of isosafrole, beta-naphthoflavone and other CYP1A inducers in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus).

The CYP1A enzyme in liver of rainbow trout (Oncorhynchus mykiss) and eelpout (Zoarces viviparus) was induced by intraperitoneal injections of isosafrole (ISF), beta-naphthoflavone (BNF), retene, 3,3',4,4'-tetrachlorobiphenyl (TCB), Clophen A50 and combinations of these compounds. The livers were sampled 5 days after injection and the microsomal fraction was used to measure the activity of CYP1A (as ethoxyresorufin-O-deethylase (EROD)) and the level of the enzyme (measured semiquantitatively as absorbance using enzyme-linked immunosorbant assay (ELISA)). Induction of CYP1A above the additive effect was observed when ISF was given together with BNF or retene. It was suggested that ISF may stabilize the enzyme or its mRNA or that ISF metabolites inhibit CYP1A processing of BNF and retene, thus increasing the effective doses of these compounds in fish liver. The results indicate a need for further studies of interactions between different CYP1A inducers in fish and a comparison of CYP1A response between different fish species. These results may have implications for the use of CYP1A induction in fish as a biomarker in aquatic systems, since a high EROD activity could be due not only to the presence of one potent inducer, but to synergistic effects of two or more inducers at low concentrations.