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(T/EH070) Aryl hydrocarbon receptor activation by Imidazole compounds in rainbow trout primary hepatocytes. Navas, José1,3, Zanuy, Silvia 1, Segner, Helmut2,3, 1 3 2 ABSTRACT- Imidazole derivatives are widely used as fungicides in agriculture. Although the risks associated with high-level short-term exposure to these compounds are well documented, there is an urgent need for chronic exposure data which relate more directly to the safety of the general public and to the wild populations exposed to low doses of these fungicides. In this respect, the induction of cytochromes P4501A (CYP1A) is considered to be one of the most sensitive and subtle cellular responses. In particular the CYP1A is induced by a wide range of environmentally dangerous compounds. Normally it has been assumed that the compounds inducing this CYP1A have some structural similarities. They are planar, aromatic, polycyclic compounds such as dioxins, polycyclic aromatic hydrocarbons, polychlorinated biphenyls and isoflavonoids such as Key words: aryl hydrocarbon receptor, imidazole, cyp1a, rainbow trout |
-naphthoflavone. The induction of the CYP1A is mediated by the binding of these compounds to the aryl hydrocarbon receptor (AhR) and the subsequent activation of this receptor. In mammals, it has been observed that imidazole compounds are also able to induce CYP1A, although they do not fulfill the structural requirements of CYP1A prototype inducers. In the present work, rainbow trout hepatocytes were isolated and maintained in culture. 24 hours after isolation, the hepatocytes were exposed to range concentrations of various imidazole compounds during three days. At the end of the exposure period, the measurements of the CYP1A dependent ethoxyresorufin-O-deethylase (EROD) activity and results of RT-PCR showed that imidazole compounds are inducers of CYP1A. The co-treatement of the cells with imidazoles and alfa-naphthoflavone (an AhR antagonist) did not affect neither the EROD activity, nor the CYP1A mRNA levels induced by the imidazole compounds. The results suggest that imidazole compounds induce CYP1A not via binding to the AhR.