Genetic and Molecular Aspects of 2,3,7,8-Tetra-Chlorodibenzo-P-Dioxin Action

The aryl hydrocarbon receptor constitutively represses c-myc transcription in human mammary tumor cells

“…The activated AhR complex then binds promoter regions of target genes at specific DNA-binding sites (aryl hydrocarbon response elements (AhREs)), thereby modulating gene transcription (Okey et al, 1994;Hankinson, 1995;Porter et al, 2001). A common outcome of AhR activation is the induction of genes such as those encoding the cytochrome P-4501A1, 1A2, and 1B1 monooxygenases (Poland et al, 1974;Whitlock, 1990;Carrier et al, 1992;Larsen et al, 1997). AhR-dependent upregulation of these enzymes results in increased metabolism of some AhR ligands such as PAH and the production of carcinogenic intermediates (Buters et al, 1999;Dertinger et al, 2001).…”

Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse

“…These groups of chemicals cause various toxicological and biological responses, typified by teratogenesis, thymic atrophy, severe epithelial disorders, wasting syndrome, tumor promotion, and induction of xenobiotic-metabolizing enzymes in experimental animals (1,2). The toxicities of these compounds are mediated by a conserved signaling pathway (1-4) through binding to and activation of the arylhydrocarbon receptor (AHR).…”

Interaction between Oxidative Stress Sensor Nrf2 and Xenobiotic-activated Aryl Hydrocarbon Receptor in the Regulation of the Human Phase II Detoxifying UDP-glucuronosyltransferase 1A10

“…Upon ligand binding (e.g. 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD), phytochemicals, and sterols) the AhR ligand complex translocates into the nucleus and dimerizes with the Arnt (aryl hydrocarbon receptor nuclear translocator) (25). The AhR/Arnt dimer binds to XRE DNA-binding motifs located in the promoter of many drug-metabolizing enzymes.…”