Use of cultured cells in the identification of potential teratogens.
An agent can be teratogenic either if it preferentially affects specific differentiating cell types or if it acts on all cells, differentiating cells being particularly vulnerable. The general effect is more easily revealed because it also causes cell death or growth inhibition, phenomena that can be measured in cell cultures. The concentration that an administered teratogen reaches in the embryo can be measured in rodents. Such biologic results as well as measurements of physicochemical constants (partition coefficients, pK values), uptake rates, cell surface binding constants, and the inhibition of specific biochemical reactions can be correlated with each other, thereby enabling one to predict the potential teratogenicity of a new compound. The probability with which such a prediction is valid for humans (and the price of the investigation) increases with the use of physical, chemical, biochemical, and cellular test systems, and is highest if the gestating mammal is used. For the evaluation of large numbers of compounds, such a tier approach seems necessary. Measurements on the effects of lipophilic acids are mentioned in more detail.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004353:Drug Evaluation, Preclinical / Q000379:methods; D012995:Solubility; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens