Molecular biology of the Ah receptor and its role in carcinogenesis

The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear transcrip tion factor that mediates responses to toxic halogenated aromatic toxins su ch as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polynuclear aromatic hydr ocarbons, combustion products, and numerous phytochemicals such as flavonoi ds and indole-3-carbinol (I3C). The nuclear AhR complex is a heterodimer co ntaining the AhR and AhR nuclear translocator (Arnt) proteins, and the mole cular mechanism of AhR action is associated with binding of the heterodimer to dioxin responsive elements (DREs) in regulatory regions of Ah-responsiv e genes. TCDD, a 'xenodioxin', is a multi-site carcinogen in several specie s and possibly in humans, whereas natural AhR ligands including I3C and fla vonoids tend to protect against cancer. Both TCDD and phytochemicals inhibi t estrogen-induced breast and endometrial cancer, and the molecular mechani sms of this common response will be described. (C) 2001 Elsevier Science Ir eland Ltd. All rights reserved.