HUMAN DIOXIN RECEPTOR CHIMERA TRANSACTIVATION IN A YEAST MODEL SYSTEMAND STUDIES ON RECEPTOR AGONISTS AND ANTAGONISTS

A yeast dioxin receptor chimera model has been developed to study liga nd binding and transactivation properties of the human dioxin receptor . Using this new yeast model, the human dioxin receptor chimera was fo und to possess a constitutive transactivity on a LacZ reporter gene, h owever, the transactivation by the chimera was enhanced by the additio n of several polycyclic aromatic hydrocarbons to the culture medium. T he order of best polycyclic aromatic hydrocarbon inducer to worst corr elated well with the known in vitro dioxin receptor binding affinities for these polycyclic aromatic hydrocarbons. 7,8-Benzoflavone, a weak dioxin receptor agonist and strong antagonist of the mammalian dioxin receptor also behaved as a weak agonist and strong antagonist of the h uman dioxin receptor chimera expressed in yeast. The implications for these findings as well as the utility of this new yeast human dioxin r eceptor chimera model are discussed.