C. Deheer et al., TOXICITY OF 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN (TCDD) TO THE HUMAN THYMUS AFTER IMPLANTATION IN SCID MICE, Toxicology and applied pharmacology, 134(2), 1995, pp. 296-304
There are conflicting data with regard to the sensitivity of the human
immune system to the toxic action of the highly toxic environmental p
ollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). SCID mice engraft
ed with human fetal thymus and liver tissue fragments (SCID-hu mice),
which sustain normal human T cell differentiation in the thymus graft,
were used to directly assess the sensitivity of the human thymus for
TCDD. Wistar rats and SCID-hu mice were exposed to 1, 5, or 25 mu g TC
DD/kg body weight. Histopathologic effects were evaluated for rat thym
us and transplanted human thymus on Day 4 after exposure. The relative
size of the cortex showed a dose-dependent decrease in both the norma
l rat thymus and grafted human thymus (significant at 25 mu g/kg). SCI
D-ra mice (SCID mice with a fetal rat thymus and liver graft) were use
d as an intermediate model between the normal rat and SCID-hu mice, an
d were exposed to the same dose levels of TCDD. However, 90% of the SC
ID-ra mice developed a cutaneous graft-versus-host reaction, associate
d with lymphodepletion of the rat thymus grafts, and hence a limited n
umber of SCID-ra mice were available for evaluation of TCDD effects. T
he data obtained in SCID-ra mice were in line with those in normal rat
and grafted human thymus. In gas chromatography/ mass spectrometry an
alysis, TCDD tissue concentrations in the normal rat thymus and grafte
d human thymus were similar. We conclude that the human thymus serves
as a target for TCDD, and that the human thymus and the Wistar rat thy
mus display a comparable sensitivity to the toxic action of TCDD. (C)
1995 Academic Press, Inc.