Reduced activity of tryptophan 2,3-dioxygenase in the liver of rats treated with chlorinated dibenzo- p-dioxins (CDDs): Dose-responses and structure-activity relationship

Abstract

The activity of tryptophan 2,3-dioxygenase (TdO) was measured in the livers of male Sprague-Dawley rats after acutely toxic doses (LD 20–LD 80) of chlorinated dibenzo- p-dioxins (CDDs) with 4 of the up to 7 chlorine substituents occupying the 2,3,7,8-positions. Treatment with toxic doses of CDDs results in voluntary feed refusal of rats. A corresponding involuntary reduction of feed intake in naive animals (pair-feeding) causes elevated levels of TdO activity. In the CDD treated rats, however, TdO activities were dose-dependently reduced. An LD 80 reduced TdO activity to about 50% of the level found in the corresponding pair-fed animals. This decrease of TdO activity explains the dose-dependent increase of serum tryptophan, which in turn is the likely cause of voluntary feed refusal observed in CDD-treated rats. The activity of another enzyme which is regulated in a fashion very similar to that of TdO, viz., tyrosine aminotransferase (TAT), was consistently, but not dose-dependently, affected by treatment with CDDs.