The interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 6-methyl-1,3,8-trichlorodibenzofuran in chick embryo hepatocytes.
Treatment of chick embryo hepatocytes in ovo and in culture with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) resulted in a dose-dependent induction of microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities. Significant induction was observed in the hepatocytes at TCDD doses as low as 10(-11) mol/egg (in ovo) and 10(-10)m (in culture). In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was a relatively weak inducer of these activities and only 10-20% of the induction responses observed for TCDD were elicited by MCDF at doses of 10(-6) mol/egg or 10(-7)m in culture. Co-treatment of the chick embryo hepatocytes with TCDD (10(-10) mol/egg in ovo; 10(-10)m in culture) and different concentrations of MCDF (10(-6) to 10(-8) mol/egg in ovo and 10(-7) and 10(-8)m in culture) resulted in minimal inhibition of TCDD-induced enzyme activities in ovo and a 37 to 50% inhibition in culture. The partial antagonist activity of MCDF in the chick embryo hepatocytes in culture paralleled the interactive effects previously reported in rodent liver and transformed rodent cell lines. TCDD (10(-7) to 10(-10)m) also caused an accumulation of hepta- and octacarboxyporphyrins in chick embryo hepatocytes (10(-7) to 10(-9)m); however, MCDF (10(-6) and 10(-5)m) elicited similar responses and MCDF did not significantly decrease the TCDD-induced porphyrogenic response in these cells. These results suggest that chick embryo hepatocytes in culture will serve as a useful model for investigating TCDD-induced gene transcription and the effects and mechanism of action of antagonists.
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Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843-4466, USA.
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