Abstract
Several in vitro cellular systems designed to screen agents for teratogenic potential are described in this report. These assays were selected from a review of literature published through the spring of 1986 that generated over 100 references on teratological research using cell-based systems. Some of the assays have a broader application than others, but most require confirmation by one or more additional complementary tests because of the specificity of the teratogenic mechanism the assays are investigating. Included are systems that use analysis of tumor cell attachment; intercellular communication; growth of human embryonic palatal mesenchyme cells; progesterone production in porcine granulosa cells; differentiation of embryonic neural crest, limb bud, midbrain, and Drosophila cells; and differentiation of tumor cells. Because of the dynamic nature of cell culture work, the group of assays listed here should not be viewed as encompassing all cell systems of value with regard to teratogenicity testing; instead, the list represents several of the more prominent systems now being evaluated by the scientific community.
Full text
PDF










Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahrens P. B., Solursh M., Reiter R. S. Stage-related capacity for limb chondrogenesis in cell culture. Dev Biol. 1977 Oct 1;60(1):69–82. doi: 10.1016/0012-1606(77)90110-5. [DOI] [PubMed] [Google Scholar]
- Ames B. N., Mccann J., Yamasaki E. Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975 Dec;31(6):347–364. doi: 10.1016/0165-1161(75)90046-1. [DOI] [PubMed] [Google Scholar]
- Bournias-Vardiabasis N., Teplitz R. L., Chernoff G. F., Seecof R. L. Detection of teratogens in the Drosophila embryonic cell culture test: assay of 100 chemicals. Teratology. 1983 Aug;28(1):109–122. doi: 10.1002/tera.1420280114. [DOI] [PubMed] [Google Scholar]
- Bournias-Vardiabasis N., Teplitz R. L. Use of Drosophila embryo cell cultures as an in vitro teratogen assay. Teratog Carcinog Mutagen. 1982;2(3-4):333–341. doi: 10.1002/1520-6866(1990)2:3/4<333::aid-tcm1770020315>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]
- Braun A. G., Buckner C. A., Emerson D. J., Nichinson B. B. Quantitative correspondence between the in vivo and in vitro activity of teratogenic agents. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2056–2060. doi: 10.1073/pnas.79.6.2056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Braun A. G., Emerson D. J., Nichinson B. B. Teratogenic drugs inhibit tumour cell attachment to lectin-coated surfaces. Nature. 1979 Nov 29;282(5738):507–509. doi: 10.1038/282507a0. [DOI] [PubMed] [Google Scholar]
- Braun A. G., Nichinson B. B., Horowicz P. B. Inhibition of tumor cell attachment to concanavalin A-coated surfaces as an assay for teratogenic agents: approaches to validation. Teratog Carcinog Mutagen. 1982;2(3-4):343–354. doi: 10.1002/1520-6866(1990)2:3/4<343::aid-tcm1770020316>3.0.co;2-s. [DOI] [PubMed] [Google Scholar]
- Buzin C. H., Bournias-Vardiabasis N. Teratogens induce a subset of small heat shock proteins in Drosophila primary embryonic cell cultures. Proc Natl Acad Sci U S A. 1984 Jul;81(13):4075–4079. doi: 10.1073/pnas.81.13.4075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flint O. P. A micromass culture method for rat embryonic neural cells. J Cell Sci. 1983 May;61:247–262. doi: 10.1242/jcs.61.1.247. [DOI] [PubMed] [Google Scholar]
- Flint O. P., Orton T. C. An in vitro assay for teratogens with cultures of rat embryo midbrain and limb bud cells. Toxicol Appl Pharmacol. 1984 Nov;76(2):383–395. doi: 10.1016/0041-008x(84)90020-6. [DOI] [PubMed] [Google Scholar]
- Flint O. P., Orton T. C., Ferguson R. A. Differentation of rat embryo cells in culture: response following acute maternal exposure to teratogens and non-teratogens. J Appl Toxicol. 1984 Apr;4(2):109–116. doi: 10.1002/jat.2550040211. [DOI] [PubMed] [Google Scholar]
- Greenberg J. H. Detection of teratogens by differentiating embryonic neural crest cells in culture: evaluation as a screening system. Teratog Carcinog Mutagen. 1982;2(3-4):319–323. doi: 10.1002/1520-6866(1990)2:3/4<319::aid-tcm1770020313>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
- Greenberg J. H., Schrier B. K. Development of choline acetyltransferase activity in chick cranial neural crest cells in culture. Dev Biol. 1977 Nov;61(1):86–93. doi: 10.1016/0012-1606(77)90344-x. [DOI] [PubMed] [Google Scholar]
- Guntakatta M., Matthews E. J., Rundell J. O. Development of a mouse embryo limb bud cell culture system for the estimation of chemical teratogenic potential. Teratog Carcinog Mutagen. 1984;4(4):349–364. doi: 10.1002/tcm.1770040405. [DOI] [PubMed] [Google Scholar]
- Haney A. F., Hughes S. F., Hughes C. L., Jr Screening of potential reproductive toxicants by use of porcine granulosa cell cultures. Toxicology. 1984 Apr 2;30(3):227–241. doi: 10.1016/0300-483x(84)90094-5. [DOI] [PubMed] [Google Scholar]
- Haney A. F., Schomberg D. W. Steroidal modulation of progesterone secretion by granulosa cells from large porcine follicles: a role for androgens and estrogens in controlling steroidogenesis. Biol Reprod. 1978 Sep;19(2):242–248. doi: 10.1095/biolreprod19.2.242. [DOI] [PubMed] [Google Scholar]
- Hascall V. C., Oegema T. R., Brown M., Caplan A. I. Isolation and characterization of proteoglycans from chick limb bud chondrocytes grown in vitro. J Biol Chem. 1976 Jun 10;251(11):3511–3519. [PubMed] [Google Scholar]
- Hassell J. R., Horigan E. A. Chondrogenesis: a model developmental system for measuring teratogenic potential of compounds. Teratog Carcinog Mutagen. 1982;2(3-4):325–331. doi: 10.1002/1520-6866(1990)2:3/4<325::aid-tcm1770020314>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- Hassell J. R., Pennypacker J. P., Lewis C. A. Chondrogenesis and cell proliferation in limb bud cell cultures treated with cytosine arabinoside and vitamin A. Exp Cell Res. 1978 Mar 15;112(2):409–417. doi: 10.1016/0014-4827(78)90223-9. [DOI] [PubMed] [Google Scholar]
- Hooper M. L., Subak-Sharpe J. H. Metabolic cooperation between cells. Int Rev Cytol. 1981;69:45–104. doi: 10.1016/s0074-7696(08)62320-7. [DOI] [PubMed] [Google Scholar]
- Kochhar D. M. The use of in vitro procedures in teratology. Teratology. 1975 Jun;11(3):273–287. doi: 10.1002/tera.1420110307. [DOI] [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- May J. V., McCarty K., Jr, Reichert L. E., Jr, Schomberg D. W. Follicle-stimulating hormone-mediated induction of functional luteinizing hormone/human chorionic gonadotropin receptors during monolayer culture of porcine granulosa cells. Endocrinology. 1980 Oct;107(4):1041–1049. doi: 10.1210/endo-107-4-1041. [DOI] [PubMed] [Google Scholar]
- Mummery C. L., van den Brink C. E., van der Saag P. T., de Laat S. W. A short-term screening test for teratogens using differentiating neuroblastoma cells in vitro. Teratology. 1984 Apr;29(2):271–279. doi: 10.1002/tera.1420290213. [DOI] [PubMed] [Google Scholar]
- Mummery C. L., van den Brink S., van der Saag P. T., de Laat S. W. Screening for cytotoxicity in neuroblastoma cells. I. Dependence of growth inhibition on the presence of serum. Toxicol Lett. 1983 Sep;18(3):201–209. doi: 10.1016/0378-4274(83)90094-2. [DOI] [PubMed] [Google Scholar]
- Pratt R. M., Grove R. I., Willis W. D. Prescreening for environmental teratogens using cultured mesenchymal cells from the human embryonic palate. Teratog Carcinog Mutagen. 1982;2(3-4):313–318. doi: 10.1002/1520-6866(1990)2:3/4<313::aid-tcm1770020312>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
- Pratt R. M., Willis W. D. In vitro screening assay for teratogens using growth inhibition of human embryonic cells. Proc Natl Acad Sci U S A. 1985 Sep;82(17):5791–5794. doi: 10.1073/pnas.82.17.5791. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schubert D., Humphreys S., Jacob F., de Vitry F. Induced differentiation of a neuroblastoma. Dev Biol. 1971 Aug;25(4):514–546. doi: 10.1016/0012-1606(71)90004-2. [DOI] [PubMed] [Google Scholar]
- Trosko J. E., Chang C. C., Netzloff M. The role of inhibited cell-cell communication in teratogenesis. Teratog Carcinog Mutagen. 1982;2(1):31–45. doi: 10.1002/1520-6866(1990)2:1<31::aid-tcm1770020105>3.0.co;2-2. [DOI] [PubMed] [Google Scholar]
- Welsch F., Stedman D. B., Carson J. L. Effects of a teratogen on [3H]uridine nucleotide transfer between human embryonal cells and on gap junctions. Exp Cell Res. 1985 Jul;159(1):91–102. doi: 10.1016/s0014-4827(85)80040-9. [DOI] [PubMed] [Google Scholar]
- Welsch F., Stedman D. B. Inhibition of metabolic cooperation between Chinese hamster V79 cells by structurally diverse teratogens. Teratog Carcinog Mutagen. 1984;4(3):285–301. doi: 10.1002/tcm.1770040304. [DOI] [PubMed] [Google Scholar]
- Wilk A. L., Greenberg J. H., Horigan E. A., Pratt R. M., Martin G. R. Detection of teratogenic compounds using differentiating embryonic cells in culture. In Vitro. 1980 Apr;16(4):269–276. doi: 10.1007/BF02618331. [DOI] [PubMed] [Google Scholar]
- Yoneda T., Pratt R. M. Mesenchymal cells from the human embryonic palate are highly responsive to epidermal growth factor. Science. 1981 Jul 31;213(4507):563–565. doi: 10.1126/science.7017936. [DOI] [PubMed] [Google Scholar]
- Yotti L. P., Chang C. C., Trosko J. E. Elimination of metabolic cooperation in Chinese hamster cells by a tumor promoter. Science. 1979 Nov 30;206(4422):1089–1091. doi: 10.1126/science.493994. [DOI] [PubMed] [Google Scholar]
- de Laat S. W., van der Saag P. T. The plasma membrane as a regulatory site in growth and differentiation of neuroblastoma cells. Int Rev Cytol. 1982;74:1–54. doi: 10.1016/s0074-7696(08)61168-7. [DOI] [PubMed] [Google Scholar]
