Nature 282, 507 - 509 (29 November 1979); doi:10.1038/282507a0

Teratogenic drugs inhibit tumour cell attachment to lectin-coated surfaces

Andrew G. Braun, David J. Emerson & Bradley B. Nichinson

Harvard Medical School, Department of Radiation Therapy, 50 Binney Street, Boston, Massachusetts 02115

Interactions between embryonic cells are generally thought to have a central role in the control of development¹. When these morphogenic interactions are interrupted by either physical intervention² or genetic defects³, normal development is impaired. In accord with these experiments, specific interactions between embryonic cells have been demonstrated in several in vitro systems. Many investigators have described homotypic aggregation of chick embryo cells⁴⁻⁸, and heterotypic specificity has also been described⁹. Because of the importance of morphogenic cell−cell interactions in development it follows that agents that interfere with these interactions, regardless of the interference mechanism, are potential teratogens. Here we have used a simple in vitro cell to surface recognition system in an attempt to screen for potential teratogens. We have found a very high correlation between inhibitory activity in the in vitro assay and reported teratogenic activity in human or animal studies. This suggests that many teratogenic agents may act by interfering, in an as yet unknown way, in normal cell to cell interactions.

References

1.	Saxen, L. Handbook of Teratology Vol. 2 (eds Wilson, J. G. & Fraser, F. C.) 171–197 (Plenum, New York, 1977).
2.	Wartiovaara, J., Nordling, S., Lehtonen, E. & Saxen, L. J. Embryol. exp. Morph. 31, 667–682 (1974).
3.	Chase, H. B. & Chase, E. B. J. Morph. 68, 279–301 (1941).
4.	McGuire, E. J. & Burdick, C. L. J. Cell Biol. 68, 80–89 (1976).
5.	Walther, B. J., Ohman, R. & Roseman, S. Proc. natn. Acad. Sci. U.S.A. 70, 1569–1573 (1973).
6.	Umbreit, J. & Roseman, S. J. biol. Chem. 250, 9360–9368 (1975).
7.	Gottleib, D. I. & Glaser, L. Biochem. biophys. Res. Commun. 63, 815–821 (1975).
8.	Rutishauser, U., Thiery, J., Brackenbury, R., Sela, B. & Edelman, G. M. Proc. natn. Acad. Sci. U.S.A. 73, 577–581 (1976).
9.	Barbera, A. J., Marchase, R. B. & Roth, S. Proc. natn. Acad. Sci. U.S.A. 70, 2482–2486 (1973).
10.	Uriel, J. Cancer Vol. 3 (ed. Becker, F. F.) 21–55 (Plenum, New York, 1975).
11.	Rutishauser, U. & Sachs, L. J. Cell Biol. 66, 76–85 (1975).
12.	Killion, J. J. & Kollmorgen, G. M. Nature 259, 674–676 (1976).
13.	Kinzel, V., Kubler, D., Richards, J. & Stohr, M. Science 192, 487–489 (1976).
14.	Order, S. E., Donahue, V. & Knapp, R. Cancer 32, 573–579 (1973).
15.	Ryan, G. B., Unanue, E. R. & Karnovsky, M. J. Nature 250, 56–57 (1974).
16.	Schardein, J. L. Drugs as Teratogens (CRC Press, Cleveland, Ohio, 1976).
17.	Larzen, V. & Bredahl, E. Acta pharmac. tox. 24, 433–455 (1966).
18.	Thomas, D. J., Warner, S. D. & Robinson, V. B. Tox. appl. Pharmac. 29, 348–357 (1974).
19.	Ebert, A. G. Tox. appl. Pharmac. 17, 274 (1970).
20.	Semprini, M. E., D'Amicis, A. & Mariani, A. Nutr. Metab. 16, 276–284 (1974).
21.	Momie, I. W., Takacs, E. & Warkany, J. Anat. Rec. 156, 175–190 (1966).
22.	Filippi, B. Adv. Teratol. 2, 239–256 (1967).
23.	Linville, G. & Shepard, T. H. Clin. Res. 20, 281 (1972).
24.	Cutler, M. & Schneider, R. Fd Cosmet. Tox. 11, 935–942 (1973).
25.	Edelman, G. M. & Rutishauser, U. Meth. Enzym. 34, 195–225 (1974).