TCDD and thyroxine have common molecular reactivity properties which enable them to present a planar face and lateral halogens in interactions with proteins. These molecular properties are consistent with the structure-toxicity relationship of TCDD and related compounds. Polybrominated naphthalenes with four or more bromine atoms and diiodobenzens were shown to bind specifically and with high affinitity to the Ah (dioxin) receptor in rat liver cytosol. The binding results further showed little dependency on bromine substitution pattern and the toxic potency of the compound. The diiodobenzenes served as models for the accessible planar faces of thyroid hormone (possible endogenous ligands for the Ah receptor). Other studies demonstrated that dioxin toxicity is modulated by thyroid hormones and that T3/T4 combinations can mimic certain toxic effects. These results are compatible with our two receptor mechanism proposal in which the Ah receptor can modulate toxicity by controlling access to a second nuclear receptor, possibly a thyroid hormone receptor.
