Teratogenic drugs inhibit the differentiation of fetal rat limb buds grafted in athymic (nude) mice

Forelimb buds of day-14 rat fetuses were cut into pieces and transplanted subcutaneously into athymic (nude) mice. On the 7th, 9th, and 11th days after grafting, the nude mice were treated with various drugs including rat teratogens. On the 20th day, the grafted tissue was examined macroscopically and histologically. While control grafts showed substantial growth and tissue differentiation similar to that observed in vivo, the differentiation of grafts was significantly inhibited by the treatment with 5-fluorouracil, cyclophosphamide, hydroxyurea, cycloheximide, mitomycin C, caffeine, aspirin, retinol palmitate, all-trans-retinoic acid, and ascorbic acid. Hydrocortisone, tetracycline, and thalidomide did not adversely affect the differentiation of grafts. Thus, the susceptibility of transplanted rat limb buds was generally close to the teratologic sensitivity of rat fetuses in vivo. The heterotransplantation method of embryonic tissues may be useful as a new experimental system in developmental toxicology.