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In vitro screening assay for teratogens using growth inhibition of human embryonic cells
Abstract:
We have tested 35 teratogenic and 20 nonteratogenic chemicals or drugs in a short-term, in vitro assay that identifies teratogens by their ability to inhibit growth of an established line of human embryonic palatal mesenchymal cells. Only those chemicals that exhibited a dose-dependent inhibition of growth at concentrations less than 1 mM were classified as inhibitory. An Aroclor-induced rat liver S-9 system was effective in metabolizing cyclophosphamide to its teratogenic form in culture. We suggest that this assay, along with the complementary tumor cell-attachment assay of Braun et al. [Braun, A. G., Emerson, D. J. & Nichinson, B. B. (1979) Nature (London) 282, 507-509] may be useful as a short-term in vitro battery for assessment of the teratogenic potential in environmental agents and to prioritize those chemicals which merit further testing in vivo.
Insights
This study introduces a new in vitro assay using human embryonic cells to identify teratogens. The test detects chemicals that inhibit cell growth, aiding in the early detection of potential developmental toxins.
Area of Science:
- Developmental toxicology
- Cell biology
- Environmental health
Background:
- Teratogens pose risks to embryonic development.
- Existing methods for teratogen identification can be time-consuming and resource-intensive.
- Need for rapid, in vitro screening assays for teratogenic potential.
Purpose of the Study:
- To evaluate a short-term in vitro assay for identifying teratogenic chemicals.
- To assess the assay's ability to detect growth inhibition in human embryonic palatal mesenchymal cells.
- To determine if metabolic activation is necessary for teratogen detection.
Main Methods:
- Tested 35 teratogenic and 20 nonteratogenic chemicals using an in vitro assay.
- Utilized a human embryonic palatal mesenchymal cell line to assess growth inhibition.
- Employed an Aroclor-induced rat liver S-9 system for metabolic activation of cyclophosphamide.
- Classified chemicals as inhibitory based on dose-dependent growth inhibition at concentrations < 1 mM.
Main Results:
- The in vitro assay successfully identified teratogenic chemicals by their growth-inhibitory effects.
- Dose-dependent inhibition was a key criterion for classifying a chemical as inhibitory.
- The S-9 system effectively activated cyclophosphamide into its teratogenic form in culture.
Conclusions:
- The developed in vitro assay is a promising tool for screening teratogenic potential.
- This assay, potentially combined with other methods, can help prioritize chemicals for further in vivo testing.
- The assay offers a rapid and efficient approach to assessing environmental agents for developmental toxicity.