Characterization of 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) as a 2,3,7,8-TCDD antagonist in male rats: induction of monooxygenases

Treatment of male Long Evans rats with doses of MCDF up to 200 μmol/kg did not significantly induce hepatic microsomal aryl hydrocarbon hydroxylase (AHH) or ethoxyresorufin O-deethylase (EROD) activities, whereas administration of 2,3,7,8-TCDD (16 nmol/kg) caused up to a 10 to 40-fold induction of these enzymes. Cotreatment of the rats with 2,3,7,8-TCDD (16 nmol/kg) and MCDF (50 μmol/kg) resulted in the inhibition of the monooxygenase enzyme induction response over a 72 hour period. Treatment of the animals with 2,3,7,8-TCDD alone caused an initial decrease in the concentration of the cytosolic Ah receptor followed by an increase of these levels (∼2 times higher than in control rats) after 72 hours. In contrast, MCDF treatment did not alter hepatic cytosolic Ah receptor levels and in the cotreatment studies (MCDF + TCDD), the effects of 2,3,7,8-TCDD on receptor levels was inhibited. Using [³H]-2,3,7,8-TCDD (+ MCDF), the time-course accumulation of nuclear [³H]-2,3,7,8-TCDD-receptor complexes was also investigated. Surprisingly, MCDF did not decrease occupied nuclear 2,3,7,8-TCDD-Ah receptor levels.