Susceptibility to cyclophosphamide and thalidomide of fetal rat limb buds grafted in athymic (nude) mice.
Limb buds of day-14 rat fetuses were cut into pieces and transplanted into athymic (nude) mice. On the 7th and 9th days after grafting, the host nude mice were given cyclophosphamide intraperitoneally (10-120 mg/kg) or thalidomide orally (30-240 mg/kg). On the 20th day, the grafted tissue was examined macroscopically and histiologically. The grafts maintained in vehicle-treated nude mice showed considerable growth and tissue differentiation similar to in vivo. Growth and histogenesis of the grafts were significantly inhibited by treatment with cyclophosphamide (greater than or equal to 20 mg/kg). There was no indication that treatment with thalidomide (less than or equal to 240 mg/kg) adversely affects the development of grafted limbs. Thus, the susceptibility of transplanted rat limb buds to these two human teratogens was identical to the susceptibility of living rat fetuses. The heterotransplantation method of embryonic tissues may be of potential use for the study of teratogenic mechanisms and for the screening of human teratogens.
Shiota
K
K
Congenital Anomaly Research Center, Faculty of Medicine, Kyoto University, Japan.
Uwabe
C
C
Yamamoto
M
M
Arishima
K
K
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D003520:Cyclophosphamide / Q000633:toxicity*; D005552:Forelimb / Q000196:embryology / Q000254:growth & development* / Q000637:transplantation; D051379:Mice; D008819:Mice, Nude; D051381:Rats; D013723:Teratogens; D013792:Thalidomide / Q000633:toxicity*; D014183:Transplantation, Heterologous
D013723:Teratogens; D013792:Thalidomide; D003520:Cyclophosphamide