Evidence for teratogenicity of thalidomide using congenic and recombinant inbred rat strains.
Teratogenic properties of thalidomide were tested in two systems of laboratory rat strains carrying the mutant lx allele that determines the polydactyly-luxate syndrome. In agreement with our previous experiments, we have confirmed that the response of foetuses basically depends on their genotype. Foetuses of LEW/BN, +/+ genotype remained unaffected 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), which was highly significant when compared with 84 vehiculum-treated and 235 untreated controls (P < 0.001). However, in 48 SHR/RI 2, lx/lx foetuses 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 controls, P < 0.001). The mutant lx allele as well as modifying genes are involved in the response to thalidomide.
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Institute of Biology, First Faculty of Medicine, Charles University, Praha.
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D000014:Abnormalities, Drug-Induced / Q000235:genetics; D000483:Alleles; D000818:Animals; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005838:Genotype; D007274:Injections, Intraperitoneal; D017880:Limb Deformities, Congenital; D008297:Male; D011247:Pregnancy; D051381:Rats; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D011918:Rats, Inbred SHR; D013792:Thalidomide / Q000633:toxicity*
D013792:Thalidomide