title: Role of the aryl hydrocarbon receptor in cell cycle regulation.
abstract: One of the most puzzling aspects of the biological impact of polycyclic aromatic hydrocarbon compounds is that they elicit an apparently unrelated variety of toxic, teratogenic, and carcinogenic responses in exposed animals and in humans. At the cellular level, these environmental toxicants affect cell cycle regulatory mechanisms and signal transduction pathways in ways that are equally diverse and often contradictory. For example, depending on the particular cell lines studied, exposure to these compounds may lead to cell proliferation, to terminal differentiation, or to apoptosis. These effects are mediated by the aryl hydrocarbon receptor, a ligand-activated transcription factor well known for its regulatory activity on the expression of several phase I detoxification cytochrome P450 genes. Research into the molecular mechanisms of aryl hydrocarbon receptor function has uncovered a novel role for this protein during cell cycle progression. The activated receptor acts as an environmental sensor and cell cycle checkpoint that commits cells exposed to adverse environmental stimuli to arrest before the onset of DNA replication.
authors.affiliation: Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, 123 E. Shields Street, Cincinnati, OH 45267-0056, USA. alvaro.puga@uc.edu
authors.forename: Alvaro
authors.initials: A
authors.lastname: Puga
authors.forename: Jennifer
authors.initials: J
authors.lastname: Marlowe
authors.forename: Sonya
authors.initials: S
authors.lastname: Barnes
authors.forename: Ching-yi
authors.initials: CY
authors.lastname: Chang
authors.forename: Andrew
authors.initials: A
authors.lastname: Maier
authors.forename: Zongqing
authors.initials: Z
authors.lastname: Tan
authors.forename: J Kevin
authors.initials: JK
authors.lastname: Kerzee
authors.forename: Xaoqing
authors.initials: X
authors.lastname: Chang
authors.forename: Matt
authors.initials: M
authors.lastname: Strobeck
authors.forename: Erik S
authors.initials: ES
authors.lastname: Knudsen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology*; D017936:Cytochrome a Group / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity; D006801:Humans; D008024:Ligands; D010957:Plasmids / Q000235:genetics; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000502:physiology*; D016160:Retinoblastoma Protein / Q000502:physiology
chemical_list: D017936:Cytochrome a Group; D004785:Environmental Pollutants; D008024:Ligands; D011084:Polycyclic Aromatic Hydrocarbons; D018336:Receptors, Aryl Hydrocarbon; D016160:Retinoblastoma Protein