title: Toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to the human thymus after implantation in SCID mice.
abstract: There are conflicting data with regard to the sensitivity of the human immune system to the toxic action of the highly toxic environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). SCID mice engrafted 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 micrograms TCDD/kg body weight. Histopathologic effects were evaluated for rat thymus and transplanted human thymus on Day 4 after exposure. The relative size of the cortex showed a dose-dependent decrease in both the normal rat thymus and grafted human thymus (significant at 25 micrograms/kg). SCID-ra mice (SCID mice with a fetal rat thymus and liver graft) were used as an intermediate model between the normal rat and SCID-hu mice, and were exposed to the same dose levels of TCDD. However, 90% of the SCID-ra mice developed a cutaneous graft-versus-host reaction, associated with lymphodepletion of the rat thymus grafts, and hence a limited number of SCID-ra mice were available for evaluation of TCDD effects. The data obtained in SCID-ra mice were in line with those in normal rat and grafted human thymus. In gas chromatography/mass spectrometry analysis, TCDD tissue concentrations in the normal rat thymus and grafted 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 thymus display a comparable sensitivity to the toxic action of TCDD.
authors.affiliation: Laboratory for Pathology, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
authors.forename: C
authors.initials: C
authors.lastname: de Heer
authors.forename: H J
authors.initials: HJ
authors.lastname: Schuurman
authors.forename: A K
authors.initials: AK
authors.lastname: Liem
authors.forename: A H
authors.initials: AH
authors.lastname: Penninks
authors.forename: J G
authors.initials: JG
authors.lastname: Vos
authors.forename: H
authors.initials: H
authors.lastname: van Loveren
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation
chemical_list: D000072317:Polychlorinated Dibenzodioxins