Elevated binding of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 3-methylcholanthrene to the Ah receptor in hepatic cytosols from phenobarbital-treated rats and mice.

Binding of 3-methylcholanthrene (MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and other "MC-type" inducers to cytosolic Ah receptor sites is the first specific step in induction of aryl hydrocarbon hydroxylase (AHH; cytochrome P1-450) by these compounds. [3H]TCDD and [3H]MC were used as radioligands to quantitate and characterize Ah receptor in hepatic cytosols from genetically "responsive" C57BL/6J mice, genetically "nonresponsive" DBA/2J mice, and AHH-inducible Sprague-Dawley rats. Injection of 50-100 mg/kg of phenobarbital (PB) for 3 days more than doubled the concentration of Ah receptor in hepatic cytosol from Sprague-Dawley rats. In C57BL/6J mice, PB injection at 25 mg/kg X 3 days significantly increased (P less than 0.01) the Ah receptor concentration in hepatic cytosol. No cytosolic Ah receptor was detectable in hepatic cytosol from untreated DBA/2J mice, nor did any Ah receptor appear after PB treatment in this "nonresponsive" strain. Although PB significantly elevated Ah receptor in hepatic cytosols of responsive rodents, many previous studies have shown that the maximal level of AHH activity in animals given PB and an "MC-type" inducer simultaneously is additive rather than synergistic. Ah receptor concentrations can be doubled by PB treatment without doubling the subsequent AHH-induction response to "MC-type" compounds. Thus, the cytosolic Ah receptor concentration per se may not be the primary determinant of a given tissue's maximal capacity for AHH induction by "MC-type" compounds.