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.
The activity of tryptophan 2,3-dioxygenase (TdO) was measured in the livers of male Sprague-Dawley rats after acutely toxic doses (LD20-LD80) 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 LD80 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.
Weber
L W
LW
Section of Environmental Toxicology, GSF--Institut für Toxikologie, Neuherberg, Germany.
Palmer
C D
CD
Rozman
K
K
D000818:Animals; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014366:Tryptophan Oxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000378:metabolism
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D014366:Tryptophan Oxygenase; D014444:Tyrosine Transaminase; D010729:Phosphoenolpyruvate Carboxykinase (GTP)