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    Validatie van een in vitro testbatterij voor teratogeniteit van xenobiotica

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    Authors
    Piersma AH
    de Vries-Klavers CE
    Jonker M
    Type
    Report
    Language
    nl
    
    Metadata
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    Title
    Validatie van een in vitro testbatterij voor teratogeniteit van xenobiotica
    Translated Title
    Validation of an in vitro test battery for teratogenicity of xenobiotics
    Publiekssamenvatting
    Dit rapport beschrijft de validatie van twee in vitro testen voor embryotoxiciteit. De testen zijn gebaseerd op de differentiatie in kweek van embryocarcinomacellen naar mesodermale respectievelijk endodermale derivaten. Mesoderm differentiatie wordt geinduceerd door coculture met een endodermale cellijn en resulteert in foci met kloppende hartspiercellen. Endoderm differentiatie wordt geinduceerd met retinolzuur en resulteert in visceraal endoderm dat specifiek alphafoetoproteine produceert. Validatie is uitgevoerd met anti-epileptica en retinoiden. In beide testen werd de celdifferentiatie door een aantal stoffen dosis-afhankelijk geremd. De reproduceerbaarheid van beide testen liet echter te wensen over. Dit wordt vooral toegeschreven aan de variabiliteit in groei- en differentiatie van de gebruikte embryocarcinoma cellijnen. Gezien deze bevindingen lijken de gebruikte protocollen vooralsnog niet geschikt als gestandaardiseerde in vitro embryotoxiciteitstesten.<br>
    This report describes the validation of two in vitro tests for embryotoxicity. The tests are based upon the differentiation in culture of embryonal carcinoma cell lines into mesodermal or endodermal derivatives, respectively. Mesodermal differentiation is induced by coculture with an endodermal cell line and results in foci of beating heart muscle cells. Endodermal differentiation is induced with retinoic acid and results in visceral endoderm which specifically produces alphafetoprotein. Validation has been carried out with anticonvulsants and retinoids. In both tests, cell differentiation was inhibited dose-dependently by a number of compounds. However, the reproducibility of both tests was not satisfactory. This was mainly caused by the variability in growth and differentiation of the embryocarcinoma cell lines employed. In view of these findings the protocols used seem not useful so far as standardised in vitro embryotoxicity tests.<br>
    Publisher
    Rijksinstituut voor Volksgezondheid en Milieu RIVM
    Sponsors
    GZB
    VI
    URI
    http://hdl.handle.net/10029/261479
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