We have tested 74 teratogenic and 28 nonteratogenic agents in a recently developed in vitro teratogen assay system. The assay identifies teratogens by their ability to inhibit attachment of ascites tumor cells to plastic surfaces coated with concanavalin A. There is a qualitative agreement between in vivo animal data and in vitro activity for 81 of the 102 agents (79%). Quantitative analysis shows a highly significant correlation coefficient of 0.69 between the inhibitory in-vitro dose and the'lowest reported teratogenic dose for 54 of the 60 inhibitory teratogens. The doses analyzed ranged over 5 orders of magnitude. We interpret these results to mean that attachment inhibition in concert with other, complementary, in vitro assay systems can become a useful method for the assessment of the teratogenic potential of environmental agents.To be useful, in vitro assay systems for teratogenic agents should be able to provide aquarntitative estimate ofteratogenic potency *in laboratory animals or in humans. In vivo processes of absorption, placental transfer, and maternal and embryonic metabolism make it unlikely that any group ofin vitro systems will be able to predict in vivo potency precisely. However, as in vitro systems approach quantitative and qualitative correspondence with in vivo results, they will become increasingly useful in the assessment of the teratogenic risk associated with environmental agents.Our interest in the correspondence between in vitro and in vivo data stems from the need to evaluate the validity of a recently developed in vitro teratogen assay (1). Teratogens are identified in the assay by their ability to inhibit the attachment of tumor cells to plastic surfaces coated with concanavalin A. In general, nonteratogens do not inhibit attachment.The working hypothesis behind this assay system can be summarized as follows. Because morphogenic interactions play a central role in development (2), agents that interfere with these interactions can be expected to lead to aberrant development and congenital malformations. A substantial body of indirect evidence suggests that these interactions are mediated by cellto-cell or cell-to-extracellular matrix interactions involving carbohydrate to receptor binding (3-9). In vitro studies indicate that embryonic cell-to-cell interactions share several characteristics with cell attachment to lectin-coated surfaces. For example, both processes consist of two stages, the first being a passive ligand-receptor binding, and the second involving metabolic energy and cytoskeletal elements (6, 10, 11). In both cases, the involvement of cell surface carbohydrates in the interaction can be shown (12)(13)(14). These similarities suggest to us that the processes involved in both systems may be similar, although details such as specific ligands, receptors, and cell types differ. Thus, agents that interfere with the process oflectin-mediated attachment can be expected to interfere with the process involved in morphogenic interactions and, therefore, are potential ...
The attachment of tumor cells to plastic surfaces coated with concanavalin A is inhibited by agents that either increase or decrease the apparent microviscosity of the plasma membrane. Since some promoters have been reported to decrease the plasma membrane microviscosity of treated cells, we have tested whether these agents inhibit tumor cell attachment. All 13 promoters tested were found to inhibit attachment at nontoxic concentrations. The apparent microviscosity of treated plasma membrane was reduced in the 11 cases where a measurement was possible. Eight of nine nonpromoting agents did not inhibit attachment. The exception, Aroclor 1254, was inhibitory on prolonged incubation. Finally, 10 of 13 antipromoting agents were found to also inhibit attachment. The apparent membrane microviscosity was increased following treatment with these inhibitory antipromoters. Thus, a consistent feature of promoter and antipromoter treatment is an alteration of the functional and the apparent fluid properties of the plasma membrane. These characteristics may be useful in the design of an in vitro assay for promoting activities in environmental samples.
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