The effects of cytosolic receptor modulation on the AHH-inducing activity of 2,3,7,8-TCDD

Pretreatment of immature male Wistar rats or C57BL/6J inbred mice for 7 days with 2,2′,4,4′,5,5′-hexachlorobiphenyl (300-500 umol/kg) resulted in a 100 to 300% increase in hepatic levels of the cytosolic receptor protein. This PCB congener exhibits minimal binding affinity for the receptor and does not induce hepatic microsomal aryl hydrocarbon hydroxylase (AHH) or ethoxyresorufin 0-deethylase (EROD). The hepatic microsomal AHH and EROD activities of rats treated with 2,3,7,8-TCDD (0.1 ug/kg) were 240 and 140 pmol product formed/mg protein/min. In contrast, if the rats are pretreated with 2,2′,4,4′,5,5′-hexachlorobiphenyl 7 days prior to intraperitoneal injection of 2,3,7,8-TCDD (0.1 ug/kg) the hepatic AHH and EROD activities were 1400 and 2340 pmol product formed/mg protein/min. Comparable interactive effects of 2,2′,4,4′,5,5′-hexachlorobiphenyl and 2,3,7,8-TCDD were also observed in C57BL/6J mice; hepatic microsomal AHH and EROD activities of mice treated with 2,3,7,8-TCDD (0.32 ug/kg) were 340 and 437 pmol product formed/mg protein/min however these activities were increased to 587 and 1383 pmol product/mg protein/min in mice treated with both 2,3,7,8-TCDD (0.32 ug/kg) and 2,2′,4,4′,5,5t́-hexachlorobiphenyl (500 umol/kg). These synergistic effects were observed in rats and mice only at dose levels of 2,3,7,8-TCDD which elicited submaximal AHH and EROD induction responses.