The SCID-hu mouse as a tool in immunotoxicological risk assessment: effects of 2-acetyl-4(5)-tetrahydroxybutyl-imidazole (THI) and di-n-butyltin dichloride (DBTC) on the human thymus in SCID-hu mice.
SCID mice engrafted with human fetal thymus and liver tissue fragments (SCID-hu mice) are currently considered as a new tool in human immunotoxicological risk assessment. Testing of various immunotoxicants exerting thymotoxicity via different intrathymic target cell types is necessary for validation of this model. Therefore, SCID-hu mice were exposed to 2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)-imidazole (THI), the immunotoxic component in the food additive, Caramel Colour III, or the organotin compound, di-n-butyltin dichloride (DBTC). Histopathological examination of the human thymus grafts of SCID-hu mice either exposed to THI or to DBTC showed a reduction in the relative size of the thymus cortex, an effect also described in rodents. These results indicate that the human thymus is a target for the immunotoxic action of both THI and DBTC. In addition, they indicate the promising potential of the SCID-hu mouse model as a tool for human immunotoxicological risk assessment.
de Heer
C
C
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Schuurman
H J
HJ
Houben
G F
GF
Pieters
R H
RH
Penninks
A H
AH
van Loveren
H
H
D000641:Ammonia / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D002182:Candy; D002241:Carbohydrates; D005260:Female; D005505:Food Coloring Agents / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000633:toxicity*; D051379:Mice; D016513:Mice, SCID; D009930:Organic Chemicals; D009947:Organotin Compounds / Q000633:toxicity*; D018570:Risk Assessment; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000633:toxicity*; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology / Q000637:transplantation
D002241:Carbohydrates; D005505:Food Coloring Agents; D007093:Imidazoles; D007166:Immunosuppressive Agents; D009930:Organic Chemicals; D009947:Organotin Compounds; D013723:Teratogens; C569050:caramel coloring; D000641:Ammonia; C049929:2-acetyl-4(5)-tetrahydroxybutylimidazole; C020735:dibutyldichlorotin