EVIDENCE FOR TERATOGENICITY OF THALIDOMIDE USING CONGENIC AND RECOMBINANT INBRED RAT STRAINS

Teratogenic properties of thalidomide were tested in two systems of la boratory rat strains carrying the mutant lx allele that determines the polydactyly-luxate syndrome. In agreement with our previous experimen ts, we have confirmed that the response of foetuses basically depends on their genotype. Foetuses of LEW/BN, +/+ genotype remained unaffecte d following 500 or 3 x 500 mg/kg thalidomide doses (43 and 56 foetuses , respectively). In LEW/BN, +/lx foetuses these doses elicited 24% and 87% hind feet polydactyly (14/59 and 53/61 foetuses, respectively), w hich was highly significant when compared with 84 vehiculum-treated an d 235 untreated controls (P < 0.001). However, in 48 SHR/RI 2, lx/lx f oetuses both pairs of limbs were affected in an opposite way after the 500 mg/kg thalidomide dose: hind feet oligodactyly (94/96 limbs) and increased front feet polydactyly occurred (in comparison with 70 contr ols, P < 0.001). The mutant lx allele as well as modifying genes are i nvolved in the response to thalidomide.