The effects of thalidomide and two analogues on the regenerating forelimb of the newt.

Oral administration (3 mg/day) of thalidomide during the dedifferentiation and early limb-bud stages of newt forelimb regeneration produced a variety of specific limb deformities. Proximal and preaxial skeletal elements were the most severely malformed, e.g. preaxial hemimelia, severe proximal deformities, and preaxial polydactyly. Likewise, oral, daily doses (3 mg) of the teratogenic analogue, EM12, on days 7 and 8 following bilateral amputation caused the same incidence and type of forelimb abnormalities as did thalidomide. Conversely, the non-teratogenic analogue, EM87, when orally administered (3 mg/day) on days 7 and 8 post-amputation resulted in a low rate of limb deformities, similar in type to those seen in control regenerates. The type of limb deformities observed in the regenerating newt forelimb following thalidomide treatment nearly mimic those seen in the human and monkey syndromes. Therefore, the newt represents a possible model for investigating some of the problems associated with thalidomide teratogenesis.