In vitro assays for the developmental toxicity of xenobiotic compounds using differentiating embryonal carcinoma cells in culture.
Murine embryonal carcinoma (EC) cells, which resemble the undifferentiated cells of the epiblast in the blastocyst, were used to establish two in vitro assays for developmental toxicants. The target processes in the assays are the differentiation of EC cells into endodermal and mesodermal derivatives, respectively. These processes were selected because they are crucial and specific for embryogenesis, and also because EC cell differentiation has been shown to be sensitive to various compounds that are teratogenic in vivo. The usefulness of the assays was studied with five pairs of xenobiotic compounds, with chemical analogy and different in vivo teratogenicity within each pair. Results for imidazoles and pyridines correlated well with known effectiveness in vivo; however, this was not the case for phthalates, sulfonamides and xanthines, which for the latter two is explicable in terms of mechanisms of action in vivo. Validation of the assays for classes of related compounds will determine their usefulness as a screen for each class, depending on the mechanism of action and physical properties. In this way in vitro assays will contribute to the refinement of testing, in addition to the more efficient use of laboratory animals.
Piersma
A H
AH
Unit Teratology, Endocrinology and Perinatal Screening, National Institute for Public Health and Environmental Protection, PO Box 1, 3720 BA Bilthoven, The Netherlands.
Haakmat
A S
AS
Hagenaars
A M
AM