Teratogenic potency of valproate analogues evaluated by quantitative estimation of cellular morphology in vitro

Toxicology in Vitro : an International Journal Published in Association with BIBRA
V BerezinE Bock

Abstract

To develop a simple prescreening system for teratogenicity testing, a novel in vitro assay was established using computer assisted microscopy allowing automatic delineation of contours of stained cells and thereby quantitative determination of cellular morphology. The effects of valproic acid (VPA) and analogues with high as well as low teratogenic activities-(as previously determined in vivo)-were used as probes for study of the discrimination power of the in vitro model. VPA, a teratogenic analogue (+/-)-4-en-VPA, and a non-teratogenic analogue (E)-2-en-VPA, as well as the purified (S)- and (R)-enantiomers of 4-yn-VPA (teratogenic and non-teratogenic, respectively), were tested for their effects on cellular morphology of cloned mouse fibroblastoid L-cell lines, neuroblastoma N2a cells, and rat glioma BT4Cn cells, and were found to induce varying increases in cellular area: Furthermore, it was demonstrated that under the chosen conditions the increase in area correlated statistically significantly with the teratogenic potency of the employed compounds. Setting the cellular area of mouse L-cells to 100% under control conditions, the most pronounced effect was observed for (S)-4-yn-VPA (211%, P = < 0.001) followed by VPA (186%, ...Continue Reading

References

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Citations

Mar 6, 2004·Neurotoxicology and Teratology·Helen C GallagherCiaran M Regan
May 8, 2004·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Peter S WalmodElisabeth Bock
Mar 10, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·G O'LearyC M Regan
Jan 10, 1997·Toxicology in Vitro : an International Journal Published in Association with BIBRA·E O'Brien, C M Regan
Oct 29, 2002·Reproductive Toxicology·Leah C FullerDarrell J Wiens
Dec 5, 1998·European Journal of Cell Biology·S FennrichB Schlosshauer
May 29, 2002·Toxicology and Applied Pharmacology·Peter S WalmodElisabeth Bock
Dec 11, 1999·Biochimica Et Biophysica Acta·P ThomsenB Norrild
Jul 25, 1998·Cell Motility and the Cytoskeleton·P S WalmodV Berezin
Dec 24, 1997·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·C L BaconC M Regan

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