Interaction of diuron and related substituted phenylureas with the Ah receptor pathway

Bin Zhao, David S. Baston, Bruce Hammock, Michael S. Denison

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that mediates many of the biological and lexicological actions of structurally diverse chemicals, including the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin. Here, we have examined the ability of diuron, a widely used herbicide, and several structurally related substituted phenylureas to bind to and activate/inhibit the AhR and AhR signal transduction. Diuron induced CYP1A1 mRNA levels in mouse hepatoma (Hepa1c1c7) cells and AhR-dependent luciferase reporter gene expression in stably transfected mouse, rat, guinea pig, and human cell lines. In addition, ligand binding and gel retardation analysis demonstrated the ability of diuron to competitively bind to and stimulate AhR transformation and DNA binding in vitro and in intact cells. Several structurally related substituted phenylureas competitively bound to the guinea pig hepatic cytosolic AhR, inhibited 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced AhR-dependent luciferase reporter gene expression in a species-specific manner and stimulated AhR transformation and DNA binding, consistent with their role as partial AhR agonists. These results demonstrate not only that diuron and related substituted phenylureas are AhR ligands but also that exposure to these chemicals could induce/inhibit AhR-dependent biological effects.

Original languageEnglish (US)
Pages (from-to)103-113
Number of pages11
JournalJournal of Biochemical and Molecular Toxicology
Volume20
Issue number3
DOIs
StatePublished - 2006

Keywords

  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin
  • Ah Receptor
  • Diuron
  • TCDD
  • Urea herbicide

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Toxicology
  • Health, Toxicology and Mutagenesis

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