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Vol. 56, Issue 4, 784-790, October 1999
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto,
Ontario, Canada (R.F.C., I.M.R., T.S.); and Institut National de la
Santé et de la Recherche Médicale Unit 135, Hôpital
de Bicetre, Le Kremlin-Bicêtre, France (M.Q., A.J., E.M.,
J.-F.S.).
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-1
, 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.
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