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 Citations (Scopus)

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

Fingerprint

Diuron
Aryl Hydrocarbon Receptors
Ligands
Luciferases
Reporter Genes
Gene expression
Guinea Pigs
Gene Expression
Signal transduction
Cytochrome P-450 CYP1A1
DNA
Herbicides
Rats
Hepatocellular Carcinoma
Signal Transduction
Transcription Factors

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

Cite this

Interaction of diuron and related substituted phenylureas with the Ah receptor pathway. / Zhao, Bin; Baston, David S.; Hammock, Bruce; Denison, Michael S.

In: Journal of Biochemical and Molecular Toxicology, Vol. 20, No. 3, 2006, p. 103-113.

Research output: Contribution to journalArticle

Zhao, Bin ; Baston, David S. ; Hammock, Bruce ; Denison, Michael S. / Interaction of diuron and related substituted phenylureas with the Ah receptor pathway. In: Journal of Biochemical and Molecular Toxicology. 2006 ; Vol. 20, No. 3. pp. 103-113.
@article{8e085eadde6e49ebba80178f47f48cd5,
title = "Interaction of diuron and related substituted phenylureas with the Ah receptor pathway",
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.",
keywords = "2,3,7,8-Tetrachlorodibenzo-p-dioxin, Ah Receptor, Diuron, TCDD, Urea herbicide",
author = "Bin Zhao and Baston, {David S.} and Bruce Hammock and Denison, {Michael S.}",
year = "2006",
doi = "10.1002/jbt.20126",
language = "English (US)",
volume = "20",
pages = "103--113",
journal = "Journal of Biochemical and Molecular Toxicology",
issn = "1095-6670",
publisher = "John Wiley and Sons Inc.",
number = "3",

}

TY - JOUR

T1 - Interaction of diuron and related substituted phenylureas with the Ah receptor pathway

AU - Zhao, Bin

AU - Baston, David S.

AU - Hammock, Bruce

AU - Denison, Michael S.

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

KW - 2,3,7,8-Tetrachlorodibenzo-p-dioxin

KW - Ah Receptor

KW - Diuron

KW - TCDD

KW - Urea herbicide

UR - http://www.scopus.com/inward/record.url?scp=33745816405&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745816405&partnerID=8YFLogxK

U2 - 10.1002/jbt.20126

DO - 10.1002/jbt.20126

M3 - Article

C2 - 16788953

AN - SCOPUS:33745816405

VL - 20

SP - 103

EP - 113

JO - Journal of Biochemical and Molecular Toxicology

JF - Journal of Biochemical and Molecular Toxicology

SN - 1095-6670

IS - 3

ER -