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
Aug 15, 1977·Zeitschrift Für Krebsforschung Und Klinische Onkologie. Cancer Research and Clinical Oncology·O D LaerumA Haugen
Feb 1, 1992·Teratology·K EhlersH Nau
Jun 1, 1992·Teratology·D M Kochhar, J D Penner
Apr 1, 1992·Toxicology Letters·R S HauckH Nau
Dec 1, 1990·Cell and Tissue Research·W HalfterD Monard
Nov 1, 1991·Pharmacology & Toxicology·H NauK Ehlers
Jan 1, 1991·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·C Maguire, C M Regan
Jul 19, 1991·Brain Research·M L Martin, C M Regan
Jan 1, 1990·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·C M ReganD C Williams
Jun 1, 1988·Journal of Cellular Biochemistry·D R SollD Wessels
Jun 1, 1989·Journal of Neurochemistry·O NybroeE Bock
Dec 1, 1989·Journal of Neurochemistry·R ProbstmeierM Schachner
Aug 30, 1988·Brain Research·M L Martin, C M Regan
Dec 1, 1986·Environmental Health Perspectives·H Nau
Nov 18, 1985·Brain Research·C M Regan
Jun 1, 1994·Teratology·J E FisherC V Vorhees
Mar 1, 1995·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·M B MeyerK Edvardsen
Jan 1, 1994·Canadian Journal of Physiology and Pharmacology·I GuestD R Varma
Mar 1, 1994·Teratology·A L Aulthouse, D C Hitt
Apr 14, 1994·Neuroreport·K C Breen, E Ronayne
Oct 1, 1993·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·K EdvardsenE Bock
Apr 1, 1993·Computer Methods and Programs in Biomedicine·R HartmanT D Coates
Jan 1, 1993·Reproductive Toxicology·O P Flint
Jul 1, 1994·Trends in Cell Biology·K Kühn, J Eble
Citations
Mar 31, 1999·Cell Motility and the Cytoskeleton·P S WalmodE Bock
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
Oct 1, 1998·European Journal of Pharmacology·U BojicH Nau
Mar 10, 2000·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·G O'LearyC M Regan
Apr 1, 1998·Toxicology in Vitro : an International Journal Published in Association with BIBRA·C L BaconE J Williams
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
Oct 3, 2002·Journal of Neurochemistry·Christopher L BaconCiaran M Regan
Dec 5, 1998·European Journal of Cell Biology·S FennrichB Schlosshauer
Dec 24, 2003·Journal of Neurochemistry·Eamon D O'LoinsighCiaran M Regan
Mar 29, 2011·Basic & Clinical Pharmacology & Toxicology·Kamil GotfrydPeter S Walmod
May 29, 2002·Toxicology and Applied Pharmacology·Peter S WalmodElisabeth Bock
Dec 11, 1999·Biochimica Et Biophysica Acta·P ThomsenB Norrild
Nov 2, 1999·Toxicology and Applied Pharmacology·A LampenH Nau
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