EFFECT OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) ON TRYPTOPHAN AND GLUCOSE-HOMEOSTASIS IN THE MOST TCDD-SUSCEPTIBLE AND THE MOST TCDD-RESISTANT SPECIES, GUINEA-PIGS AND HAMSTERS

We have previously reported that in rats 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) lethality is associated (although not necessarily causal ly) with changes in brain serotonin (5-HT) metabolism. In the present study, we have examined whether this holds for other species by compar ing the effect of TCDD in the most TCDD-susceptible and the most TCDD- resistant species, guinea pigs and hamsters, respectively. Body weight gain of guinea pigs exposed to TCDD (0.3-2.7 mu g/kg) diminished dose dependently, while the effect was marginal in hamsters (900-4600 mu g /kg). Brain 5-hydroxyindoleacetic acid (the main metabolite of brain 5 -HT), brain tryptophan (the precursor amino acid of 5-HT), and plasma free and total tryptophan were not affected at any dose in guinea pigs . In contrast, 4 days after exposure, the levels of plasma free and to tal tryptophan were consistently increased in hamsters. These, as well as brain tryptophan, were still elevated 10 days after exposure. TCDD did not affect plasma glucose level in either species. Liver glycogen was decreased in a dose-dependent manner in TCDD-treated guinea pigs as well as in their pair-fed controls on day 10. There was no change i n liver glycogen in hamsters. The activity of the gluconeogenic enzyme , phosphoenolpyruvate carboxykinase was only depressed in hamsters by all doses of TCDD. We conclude that changes in tryptophan metabolism o r in carbohydrate homeostasis cannot explain the wide interspecies dif ferences in susceptibility to the acute lethality of TCDD, although th ey may correlate with some aspects of its toxicity in certain species.