Comparative study of aryl hydrocarbon receptor ligand activities of six chemicals in vitro and in vivo View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2008-01

AUTHORS

Kazumi Sugihara, Takashige Okayama, Shigeyuki Kitamura, Keisuke Yamashita, Mineo Yasuda, Shinichi Miyairi, Yasushi Minobe, Shigeru Ohta

ABSTRACT

The aryl hydrocarbon receptor (AhR) ligand activities of six known AhR ligands were compared in vivo and in vitro. The in vivo ligand activity was estimated in terms of induction of cytochrome P450 1A1/2 activities, i.e., ethoxyresorufin-O-dealkylase (EROD) and methoxyresorufin-O-dealkylase (MROD) activities, and in vitro ligand activity was evaluated with a recombinant yeast reporter gene assay. The test chemicals were 3-methylcholanthrene (MC), beta-naphthoflavone (beta-NF), indirubin, indigo, 3,3'-diindolylmethane (DIM) and diphenyl-p-phenylenediamine (DPPD). The first four showed potent AhR ligand activity in vitro, comparable with that of 2,3,7,8-tetrachlorodibenzo-p-dioxin, while DIM and DPPD showed weaker activity. Administration of MC and beta-NF to mice caused significant induction of EROD and MROD activities, while indirubin, indigo and DIM also induced these activities, but less potently. DPPD also induced the activities, but was toxic at higher doses. These enhancing effects were lost or greatly reduced in Ahr-null mice (Ahr (-/-)). Our results suggest that EROD and MROD activity assays are useful for evaluating the AhR ligand activity of chemicals in vivo, where the biodynamics of the chemicals plays an important role. More... »

PAGES

5-11

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00204-007-0232-3

DOI

http://dx.doi.org/10.1007/s00204-007-0232-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1013029918

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/17899013


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