Abstract
Aryl hydrocarbon receptor (AhR) ligands such as dioxin and benzo[a]pyrene are environmental contaminants with many adverse health effects, including immunosuppression, carcinogenesis, and endothelial cell damage. We show here that a wine component, resveratrol (3,5,4′-trihydroxystilbene), is a competitive antagonist of dioxin and other AhR ligands. Resveratrol promotes AhR translocation to the nucleus and binding to DNA at dioxin-responsive elements but subsequent transactivation does not take place. Resveratrol inhibits the transactivation of several dioxin-inducible genes including cytochrome P-450 1A1 and interleukin-1β, both ex vivo and in vivo. Resveratrol has adequate potency and nontoxicity to warrant clinical testing as a prophylactic agent against aryl hydrocarbon-induced pathology.
Footnotes
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Send reprint requests to: Dr. Jean-François Savouret, Institut National de la Santé et de la Recherche Médicale Unit 135, Hôpital de Bicêtre, 78 rue du Général Leclerc, Le Kremlin-Bicêtre, 94270, France. E-mail:savouret{at}infobiogen.fr
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↵1 Current affiliation: Division of Reproductive Sciences, Department of Obstetrics and Gynecology, The University of Toronto, The Toronto Hospital, General Division, Toronto, Ontario, Canada.
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This work was supported by the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer and the Faculté de Médecine Paris-Sud, and the Medical Research Council of Canada. R. F. C. was supported by a joint Medical Research Council of Canada/Institut National de la Santé et de la Recherche Médicale visiting scientist award.
- Abbreviations:
- AhR
- aryl hydrocarbon receptor
- PAH
- polycyclic aromatic hydrocarbons
- BaP
- benzo[a]pyrene
- TCDD
- 2,3,7,8-tetrachlorodibenzo-p-dioxin
- TC[1,6-3H]DD
- 2,3,7,8-tetrachloro[1,6-3H]dibenzo-p-dioxin
- DRE
- dioxin responsive element
- CAT
- chloramphenicol acetyl transferase
- TK
- thymidine kinase promoter
- α-NF
- α-naphthoflavone
- NQOR
- NAD(P)H quinone oxidoreductase
- Il-1β
- interleukin-1β
- GFP
- green fluorescent protein
- DMBA
- 7,12-dimethylbenzanthracene
- I3C
- indole-3-carbinol
- LTR
- long terminal repeat
- Received February 8, 1999.
- Accepted June 22, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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