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

Roy Bannister, Stephen Safe

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

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 KD 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.

Original languageEnglish (US)
Pages (from-to)159-169
Number of pages11
JournalToxicology
Volume44
Issue number2
DOIs
StatePublished - May 1987

Keywords

  • 2, 2, 4, 4′, 5, 5′-Hexachlorobiphenyl
  • 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin
  • Synergism

ASJC Scopus subject areas

  • Toxicology

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