THE EFFECTS OF RECEPTOR MODULATORS ON THE AHH INDUCTION ACTIVITY OF 2,3,7,8-TCDD IN C57BL/6 AND DBA/2 MICE
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abstract
Treatment of immature male C57BL/6J mice with 2,2,4,4,5,5-hexachlorobiphenyl (HCB, 100-1000 umol/kg) resulted in a 44-200% increase in levels of the 2,3,7,8-TCDD hepatic cytosolic receptor protein for up to 14 days. The increased binding was not due to an alteration of the affinity of 2,3,7,8-TCDD for the receptor as shown by Scatchard analysis. In contrast treatment of immature DBA/2 mice with 2,2,4,4,5,5-HCB did not result in increased hepatic cytosolic receptor levels which were non-detectable in the treated and untreated animals. C57BL/6 mice were pretreated with 2,2,4,4,5,5-HCB (500 umol/kg) and after 7 days 2,3,7,8-TCDD (0.32 ug/kg) was administered by i.p. injection; 14 days later the hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities were 587 and 1383 pmol product/mg protein/min respectively. In contrast, these activities were 340 and 437 pmol/mg protein/min in animals treated with only 2,3,7,8-TCDD. These synergistic effects were only seen in mice treated with submaximal enzymeinducing doses of 2,3,7,8-TCDD. Treatment of DBA/2 mice with 2,2,4,4,5,5-HCB (500 umol/kg) and varying dose levels of 2,3,7,8-TCDD (10-5000 nmol/kg) resulted in apparent synergistic AHH and EROD induction activities in mice treated with submaximal and maximal enzyme inducing doses of 2,3,7,8-TCDD. 1987.
