We compared the effects of 2,3,7,8-tetra (
TCDD), 1,2,3,7,8-penta (
PeCDD), 1,2,3,4,7,8-hexa (
HxCDD) and
1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (
HpCDD) on brain
serotonin metabolism, plasma
tryptophan and liver
tryptophan pyrrolase activity in two rat strains,
TCDD-sensitive Long-Evans (Turku AB; L-E) and
TCDD-resistant Han/Wistar (Kuopio; H/W). Previously it was shown that L-E rats exhibit the expected rank order of potency for CDDs in terms of acute toxicity with
TCDD being the most potent, followed by
PeCDD,
HxCDD and
HpCDD. In contrast, to H/W rats
HxCDD was the most toxic and
TCDD the least toxic of these congeners. In the present study, the CDDs decreased
body weight in L-E rats in the following order of potency:
TCDD >
PeCDD >
HxCDD >
HpCDD. The same rank order was recorded for elevations in brain
tryptophan and plasma free
tryptophan concentrations as well as for inhibition of the main hepatic
tryptophan metabolizing
enzyme,
tryptophan pyrrolase. By contrast, in H/W rats
HxCDD was the most effective congener in producing loss of
body weight, followed by
HpCDD,
PeCDD and
TCDD. This was also true of changes in
tryptophan homeostasis. These findings imply that in
TCDD-susceptible L-E and
TCDD-resistant H/W rats the potency of
dioxin congeners in inducing acute toxicity highly correlates with their ability to disrupt
tryptophan homeostasis. However, there may not be a direct causal relationship between
body weight loss and altered
tryptophan homeostasis, because the magnitudes of these two phenomena were not consistently parallel across the
dioxin congeners tested.