Cell proliferation, migration and CAM-dependent neurite outgrowth as developmental in vitro endpoints for screening teratogenic potential: Application to valproic acid and related analogues of varying potency

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Christopher L BaconE J Williams

Abstract

The in vivo teratogenic potential of valproic acid (VPA) and related teratogenic and non-teratogenic analogues has been correlated with their effects on specific in vitro endpoints of cell proliferation, migration and CAM-dependent neurite outgrowth, as these events are common to crucial epochs of development. The (+/-)-2-n-propyl-4-pentynoic acid [(+/-)-4-yn-VPA] and S-2-n-propyl-4-pentynoic acid [S(-)-4-yn-VPA] analogues increased the incidence of neural tube defects in mouse embryos exposed to a single dose, whereas the E-2-n-propyl-2-pentenoic acid (E-2-en-VPA) analogue and R-2-n-propyl-4-pentynoic acid [R( + )-4-yn-VPA] enantiomer were without effect. VPA and related analogues tested exerted comparable G1 phase antiproliferative effects in C6 glioma and limb bud cells in a dose range of 0-3 mM; however, their relative potency did not correlate with in vivo teratogenicity. In contrast, VPA and all teratogenic analogues, at 3 mM, inhibited neuronal cell aggregation and limb bud chondrocyte differentiation in a manner that exhibited a reasonable correlation with their in vivo teratogenicity. The teratogenic S(-)-4-yn-VPA and non-teratogenic R( + )-4-yn-VPA enantiomers exhibited a differential inhibition of primary neurone out...Continue Reading

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Citations

Mar 10, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·G O'LearyC M Regan
Jul 12, 2002·Toxicology in Vitro : an International Journal Published in Association with BIBRA·N L'HuillierR H Clothier
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Dec 5, 1998·European Journal of Cell Biology·S FennrichB Schlosshauer
Apr 14, 2009·Journal of Ethnobiology and Ethnomedicine·Rodolfo GentiliSergio Sgorbati

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