title: Phenethyl isothiocyanate, a naturally occurring phytochemical, is an antagonist of the aryl hydrocarbon receptor.
abstract: METHODS
  The aryl hydrocarbon (Ah) receptor is a ligand-activated transcription factor that is activated by many carcinogens, and its target gene products play a major role in tumour development, so that antagonists of the Ah receptor represent potential chemopreventive agents.
  
  
  RESULTS
  Experimental evidence is presented herein that phenethyl isothiocyanate (PEITC), a phytochemical present in cruciferous vegetables, is such an antagonist. PEITC was a very weak ligand to the Ah receptor, as assessed using the chemical-activated luciferase expression (CALUX) assay, and a poor inducer of CYP1A1 mRNA levels when incubated in precision-cut rat liver slices for 24 h. It antagonised effectively, however, the interaction of benzo[a]pyrene to the receptor, being capable of preventing its binding as well as displacing it from the receptor. Moreover, PEITC suppressed in concentration-dependent manner the benzo[a]pyrene-mediated rise in rat hepatic CYP1A1 mRNA levels in rat slices. Finally, PEITC antagonised the benzo[a]pyrene-mediated increase in the O-deethylation of ethoxyresorufin in both rat and human precision-cut liver slices.
  
  
  CONCLUSIONS
  It is concluded that PEITC is an effective antagonist of the Ah receptor in rat and human liver, and this potential may contribute to its established chemopreventive activity.
authors.affiliation: Molecular Toxicology Group, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK.
authors.forename: Ahmad F
authors.initials: AF
authors.lastname: Abdull Razis
authors.forename: Nattaya
authors.initials: N
authors.lastname: Konsue
authors.forename: Myrto
authors.initials: M
authors.lastname: Dervetzoglou
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Plant
authors.forename: Nick
authors.initials: N
authors.lastname: Plant
authors.forename: Costas
authors.initials: C
authors.lastname: Ioannides
mesh_terms: D000368:Aged; D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014675:Vegetables / Q000737:chemistry
chemical_list: D002273:Carcinogens; D017879:Isothiocyanates; D010078:Oxazines; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D001564:Benzo(a)pyrene; C007649:ethoxyresorufin; C058305:phenethyl isothiocyanate; D019363:Cytochrome P-450 CYP1A1