Teratogenicity testing based on the interaction with a mutant allele.
The system of congenic strains of the laboratory rat carrying the mutant allele lx which is determining the polydactyly-luxate syndrome (PLS) was used for testing teratogenicity of six compounds from different pharmacological groups (cyclophosphamide, cyadox, carbadox, imipramine, verapamil, TIA). The interaction of the mutant lx allele with cyclophosphamide was highly significant (P less than 0.001) involving both polydactyly and tibial hemimely. Significant interaction with the lx allele was also proved after cyadox and carbadox treatment when compared with lx allele penetrance in LEW/BN, +/1x heterozygotes (P less than 0.01 and 0.05). In accord with our previous experiments, the teratogenic activity of the compounds tested seems to be connected with the ability to interact with nucleic acid structure and/or function.
Bílá
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Institute of Biology, 1st Medical Faculty, Charles University, Praha.
Kren
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D000014:Abnormalities, Drug-Induced / Q000235:genetics*; D000483:Alleles; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity; D003520:Cyclophosphamide / Q000633:toxicity; D005260:Female; D005333:Fetus; D007099:Imipramine / Q000633:toxicity; D008297:Male; D009152:Mutagenicity Tests; D051381:Rats; D011917:Rats, Inbred Lew; D014700:Verapamil / Q000633:toxicity
D000900:Anti-Bacterial Agents; D003520:Cyclophosphamide; D014700:Verapamil; D007099:Imipramine