In vitro screening for anticonvulsant-induced teratogenesis: drug alteration of cell adhesivity.
Anticonvulsant-induced alteration in C6 glioma cell adhesivity has been evaluated in two independent in vitro assay systems. A centrifugal shear assay was employed to determine drug-induced change in cell-substratum adhesivity. Valproate and clonazepam were found to significantly increase cell-substratum adhesivity when cells were cultured at concentrations which were within twice their therapeutic plasma level. A second assay evaluated change in affinity for concanavalin A lectin coated surfaces to determine change in cell surface glycoconjugate expression. Valproate and clonazepam and, to a lesser extent, diazepam significantly decreased drug-exposed C6 glioma cell affinity for concanavalin A lectin coated surfaces. Valproate and clonazepam had approximate IC50 values of 0.75 mM and 75 microM, respectively. These findings are compared and discussed in relation to those obtained with an anti-proliferative assay which has been suggested to predict teratogen potential.
Maguire
C
C
Department of Pharmacology, University College, Belfield, Dublin, Ireland.
Regan
C M
CM
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity*; D002448:Cell Adhesion / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D005910:Glioma / Q000473:pathology; D051381:Rats; D013723:Teratogens / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000927:Anticonvulsants; D013723:Teratogens; D003208:Concanavalin A