title: Transcriptional suppression of cytochrome P450 genes by endogenous and exogenous chemicals.
abstract: This article is an invited report of a symposium sponsored by the Division for Drug Metabolism of the American Society for Pharmacology and Experimental Therapeutics held at Experimental Biology 2003 in San Diego, California, April 11-15, 2003. Several members of the cytochrome P450 (P450) superfamily are induced after exposure to a variety of chemical signals, and we have gained considerable mechanistic insight into these processes over the past four decades. In addition, the expression of many P450s is suppressed in response to various endogenous and exogenous chemicals; however, relatively little is known about the molecular mechanisms involved. The goal of this symposium was to critically examine our current understanding of molecular mechanisms involved in transcriptional suppression of CYP genes by endogenous and exogenous chemicals. Specific examples were drawn from the following chemical categories: polycyclic and halogenated aromatic hydrocarbon environmental toxicants, inflammatory mediators, the endogenous sterol dehydroepiandrosterone and peroxisome proliferators, and bile acids. Multiple molecular mechanisms are involved in transcriptional suppression, and these processes often involve rather complex cascades of transcription factors and other regulatory proteins. Mechanistic studies of CYP gene suppression can enhance our understanding of how organisms respond to xenobiotics as well as to perturbations in endogenous chemicals involved in maintaining homeostasis.
authors.affiliation: Department of Pharmacology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada, M5S 1A8. david.riddick@utoronto.ca
authors.forename: David S
authors.initials: DS
authors.lastname: Riddick
authors.forename: Chunja
authors.initials: C
authors.lastname: Lee
authors.forename: Anahita
authors.initials: A
authors.lastname: Bhathena
authors.forename: Yoav E
authors.initials: YE
authors.lastname: Timsit
authors.forename: Po-Yung
authors.initials: PY
authors.lastname: Cheng
authors.forename: Edward T
authors.initials: ET
authors.lastname: Morgan
authors.forename: Russell A
authors.initials: RA
authors.lastname: Prough
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Ripp
authors.forename: Kristy K Michael
authors.initials: KK
authors.lastname: Miller
authors.forename: Asmeen
authors.initials: A
authors.lastname: Jahan
authors.forename: John Y L
authors.initials: JY
authors.lastname: Chiang
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000502:physiology; D001685:Biological Factors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics*; D003687:Dehydroepiandrosterone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D018836:Inflammation Mediators / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D051379:Mice; D008954:Models, Biological; D011084:Polycyclic Aromatic Hydrocarbons / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000494:pharmacology; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D001685:Biological Factors; D065607:Cytochrome P-450 Enzyme Inhibitors; D018836:Inflammation Mediators; D011084:Polycyclic Aromatic Hydrocarbons; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D015262:Xenobiotics; D003687:Dehydroepiandrosterone; D003577:Cytochrome P-450 Enzyme System