Developmentally regulated promoters from Dictyostelium discoideum as molecular markers for testing potential teratogens.
Already very early in the course of the development of new pharmaceutically relevant drugs toxicological tests are most important. In addition to acute and chronic toxicity the estimation of the teratogenic potential is rather crucial. We have recently shown that the eukaryotic microorganism Dictyostellium discoideum is a useful organism to test the cytotoxicity of chemical compounds. Since D. discoideum is competent of undergoing both vegetative growth and development, further investigations were aimed to establish a D. discoideum-based test system which could predict possible interference of drugs with developmental programs. We developed a method which allows to detect and to quantify effects of possible teratogens on D. discoideum development. This method is based on different transgenic D. discoideum strains, each carrying a bacterial lacZ gene under the control of a distinct developmentally regulated D. discoideum promoter. Here we describe the effects of the known teratogenic compound valproic acid (VPA) on this system.
Tillner
J
J
Institut für Pharmazeutische Biologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
Winckler
T
T
Dingermann
T
T
D000818:Animals; D000927:Anticonvulsants / Q000633:toxicity; D015415:Biomarkers; D004023:Dictyostelium / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development; D005798:Genes, Bacterial; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*; D014170:Transformation, Genetic; D014635:Valproic Acid / Q000633:toxicity; D001616:beta-Galactosidase / Q000096:biosynthesis
D000927:Anticonvulsants; D015415:Biomarkers; D013723:Teratogens; D014635:Valproic Acid; D001616:beta-Galactosidase