Disease relevance of Acy3

• At doses as high as 750 to 1000 mumol/kg, 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP) did not cause fetal cleft palate, suppress the splenic plaque-forming cell response to sheep red blood cells, or induce hepatic microsomal ethoxyresorufin O-deethylase (EROD) in C57BL/6J mice [1].
• The only significant interactive effect of HCBP (500 mumol/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 [2].

High impact information on Acy3

• Thus, HCBP and I2-TCBP, like the commercial polychlorinated biphenyl mixture Aroclor 1254, were partial antagonists of TCDD action in C57BL/6J mice; however, it was also apparent from the results that Aroclor 1254 was the more effective antagonist at lower doses [1].
• Using [3H]TCDD, it was also shown that some of the effects of HCBP on TCDD-mediated cleft palate may be due to the decreased levels of TCDD found in the fetal palates after cotreatment with TCDD and HCBP [1].
• Despite the lack of activity of HCBP in eliciting any of these aryl hydrocarbon (Ah) receptor-mediated responses, competitive binding studies indicated that HCBP competitively displaced 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin (TCDD) from the murine hepatic cytosolic receptor [1].
• Treatment of C57BL/6J mice with 2,2',4,4',5,5'-hexachlorobiphenyl (HCBP, 500 mumol/kg) elevated hepatic cytosolic Ah receptor levels 82-107% for up to 14 days [2].
• Similar deacetylation of N-acetyltryptophan by acylase III was also observed [3].

References