The effects of receptor antagonists on the AHH induction activity of 2,3,7,8-TCDD in C57BL/6 and DBA/2 mice: 1,3,6,8-tetrachlorodibenzofuran

Previous studies have demonstrated that 1,3,6,8-tetrachlorodibenzofuran (TCDF) inhibited the induction of aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) in rat hepatoma H-4-II E cells in culture. 1,3,6,8-TCDF did not induce hepatic microsomal AHH or EROD at doses up to 800 umol/kg in DBA/2 mice and 200 umol/kg in C57BL/6 mice. Administration of 1,3,6,8-TCDF to the latter strain of mice resulted in induction of AHH and EROD (< 25% of maximal induction activity). Cotreatment of mDBA/2 mice with 2,3,7,8-TCDD (200 nmol/kg) and with either 50, 200 or 800 umol/kg of 1,3,6,8-TCDF resulted in 13, 39 and 18% inhibition of AHH induction and 17, 34 and 21% inhibition of EROD induction respectively. Cotreatment of the more responsive C57BL/6 mice with 2,3,7,8-TCDD (15 nmol/kg) and 1,3,6,8-TCDF (10, 50, 100, 200 or 500 umol/kg) resulted in significant inhibition (17%) of AHH and EROD induction only at a 200 umol/kg dose level. It was evident that the apparent window of antagonism for 1,3,6,8-TCDF was strain dependent.