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Abstract
Fixed aliquots of both radiolabeled [3H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and hepatic Ah receptor from C57BL/6J mice were incubated competitively at 4, 23, and 30°C with mixtures of 2,3,7,8-TCDD and several polychlorinated biphenyls (PCBs). The production of the radiolabeled receptor-ligand complex changed if the ligands were added sequentially, demonstrating that the competition between PCBs and TCDD for the Ah receptor in vitro is principally a kinetic rather than an equilibrium phenomenon and is irreversible on the time scale of our in vitro experiments. Examination of previous reports on the ability of TCDD, PCBs, and their mixtures to induce cleft palate in fetal mice suggests that the potency of receptor-ligand complexes is ligand-dependent. Receptor occupancy is not a sufficient condition for toxicity, and protection by one ligand against the toxic effect of a second, more potent one is only possible when a significant fraction of receptors is occupied.
Published Version
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