Perturbations of cellular functions integral to neural tube formation by the putative teratogen sodium valproate.
The effect of therapeutic concentrations of sodium valproate (VPA) on the cell acquisition rate and adhesive properties of glioma (C6) and neuroblastoma (Neuro-2a) cell lines was evaluated. VPA impaired the mitotic rate in neuroblastoma and glioma cells with an IC(50) value of approximately 1.0 mm, and with no apparent cytotoxicity. Using a centrifugal shear adhesion assay the glioma cells showed a 2.5-fold increase in cell-substratum adhesivity at VPA concentrations of 1 mm. This effect could not be demonstrated in the neuroblastoma cell line as these cells were inherently more adhesive than the glioma cells. However, the neuroblastoma cells assumed a differentiated phenotype when cultured in the presence of 1 mm-VPA and extended numerous fibres with branching points. These findings are related to the ability of VPA to induce neural tube defects.
Martin
M L
ML
Department of Pharmacology, University College, Belfield, Dublin 4, EireUSA.
Breen
K C
KC
Regan
C M
CM