Chapter 7: Aryl Hydrocarbon Receptor Targeted by Xenobiotic Compounds and Dietary Phytochemicals Check Access

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates the toxic effects of halogenated aromatic hydrocarbons (HAHs) such as polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and select polychlorinated biphenyls (PCBs). Detectable levels of these contaminants are present in all humans. The most toxic compound in the class is 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD or dioxin). Laboratory animals exposed to environment levels of TCDD exhibit a wide spectrum of toxic responses, including increases in a number of different cancers. It is estimated that 90% of human exposure to these compounds is through dietary intake of products from animal origin and fish. AhR also exhibits profound ligand binding promiscuity, binding a number of compounds including phytochemicals such as polyphenols and flavonoids, many of which act as AhR antagonists. The presence of AhR-binding phytochemicals in the diet may in some cases antagonize the toxic effects of AhR-activating food contaminants. In this chapter we discuss the signalling pathways, the molecular mechanisms and potential health effects of activation of AhR by the dioxin-like food contaminants as well as the potential beneficial effects of AhR-modulating phytochemicals.