Evidence for teratogenicity of thalidomide using congenic and recombinant inbred rat strains

Folia Biol (Praha). 1994;40(4):161-71.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced* / genetics
  • Alleles
  • Animals
  • Embryonic and Fetal Development / drug effects*
  • Female
  • Fetus / drug effects*
  • Genotype
  • Injections, Intraperitoneal
  • Limb Deformities, Congenital
  • Male
  • Pregnancy
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • Rats, Inbred SHR
  • Thalidomide / toxicity*

Substances

  • Thalidomide