Studies on the mechanism of action of halogenated aromatic hydrocarbons

The halogenated aromatic hydrocarbons (dibenzo-p-dioxins, dibenzofurans, azo[xy]benzenes and biphenyls), a group of toxic chemicals in the environment, (a) are approximate isostereomers; (b) produce a similar pattern of biologic responses and (c) appear to act by a common mechanism. These compounds reversibly bind to a soluble receptor protein to initiate a coordinate gene expression, analogous to the action of steroid hormones. This receptor controls two distinct and dissociable pleiotropic responses: (a) the induction of microsomal monooxygenase activity and other drug metabolizing enzymes and (b) morphologic (i.e. toxic) changes, many of which involve altered cell proliferation and/or differentiation in epithelial tissues.