Synergistic interactions of 2, 3, 7, 8-TCDD and 2, 2′, 4, 4′, 5, 5′-hexachlorobiphenyl in C57BL/6J and DBA/2J mice: Role of the Ah receptor

Treatment of C57BL/2J mice with 2, 2′, 4, 4′, 5, 5′-hexachlorobiphenyl (HCBP, 500 μmol/kg) elevated hepatic cytosolic Ah receptor levels 82-107% for up to 14 days. Scatchard analysis of the [³H] 2, 3, 7, 8-TCDD (TCDD)-Ah receptor saturation binding curves from corn oil and HCBP treated rats gave K_D values of 0.80 and 0.90 nM, respectively and confirmed that treatment with HCPB did not significantly alter receptor-radioligand affinities. Administration of HCBP to DBA/2J mice did not result in detectable hepatic cytosolic Ah receptor levels. Cotreatment of C57BL/6J mice with HCBP (500 μmol/kg) at a dose level of TCDD (1 nmol/kg) which elicite less that 10% of the maximum inductions response resulted in significant synergistic iduction of hepatic EROD and AHH [compared to animals treated only with TCDD (1 nmol/kg)]. In contrast, contreatment of C57BL/6J mice with HCBP (500 μmol/kpg) and maximally inducing dose levels of TCDD (100 or 500 nmol/kg) resulted in either a slight or no difference in the induction of AHH or EROD compared to the induction responses observed in mice treated only with TCDD. In contrast, contreatment of DBA/2J mice with TCDD and HCBP (500/gmmol/kg) resulted in significant synergistic induction of AHH and EROD at both submaximal (10-50 nmol/kg) and maximal (5000 nmol/kg) induction levels of TCDD. The only significant interactive effect of HCBP (500 μmol/levels of TCDD. The only significant interactive effect of HCBP (500 μmol/kg) on the toxicity of TCDD in C57BL/6J and DBA/2J was protection from body weight loss observed after cotreatment of HCBP and TCDD in DBA/2J mice.