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DOI 10.1002/etc.5620220422
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Title (Primary) Induction of CYPIA by the N-imidazole derivative, 1-benzylimidazole
Author Navas, J.M.; Chana, A.; Herradón, B.; Segner, H.
Source Titel Environmental Toxicology and Chemistry
Year 2003
Department OEC; COE
Volume 22
Issue 4
Page From 830
Page To 836
Language englisch
Keywords Cytochrome P4501A; Imidazole; Aryl hydrocarbon receptor; Rainbow trout; Hepatocyte

Xenobiotics can induce cytochrome P4501A (CYP1A) by ligand binding to the aryl hydrocarbon receptor (AhR). Typical AhR ligands are polycyclic aromatic compounds with planar molecular conformation. The present work investigated the ability of the N-imidazole derivative, 1-benzylimidazole (BIM), to induce CYP1A in rainbow trout hepatocytes. Benzylimidazole increased hepatocellular CYP1A catalytic activity (determined as 7-ethoxyresorufin-O-deethylase [EROD] activity) and CYP1A mRNA in a concentration-dependent way. Computational studies on the molecular structure of BIM indicated that the energetically most stable BIM conformer has the imidazole ring and the phenyl ring in different planes, i.e., does not take a planar conformation. This property of BIM does not agree with the structural requirements of a typical AhR ligand. In line with this observation, we found that the AhR antagonist, alpha-naphthoflavone (alphaNF), was not able to inhibit BIM induction of EROD activity and CYP1A mRNA, although it inhibited the induction of CYP1A by the prototypic AhR ligand, alpha-naphthoflavone (betaNF). The results suggest that transcriptional activation of CYP1A by the N-imidazole derivative, BIM, is not mediated through direct ligand binding to the AhR.

Persistent UFZ Identifier
Navas, J.M., Chana, A., Herradón, B., Segner, H. (2003):
Induction of CYPIA by the N-imidazole derivative, 1-benzylimidazole
Environ. Toxicol. Chem. 22 (4), 830 - 836 10.1002/etc.5620220422