Tillner J, Winckler T, Dingermann T
Institut für Pharmazeutische Biologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany.
Pharmazie. 1996 Nov;51(11):902-6.
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.
在新型药学相关药物的研发过程中，毒理学测试在很早阶段就极为重要。除了急性和慢性毒性外，致畸潜力的评估相当关键。我们最近表明，真核微生物盘基网柄菌是一种用于测试化合物细胞毒性的有用生物体。由于盘基网柄菌既能进行营养生长又能发育，进一步的研究旨在建立一个基于盘基网柄菌的测试系统，该系统可以预测药物对发育程序可能产生的干扰。我们开发了一种方法，可检测和量化可能的致畸剂对盘基网柄菌发育的影响。该方法基于不同的转基因盘基网柄菌菌株，每个菌株在一个独特的、受发育调控的盘基网柄菌启动子控制下携带一个细菌lacZ基因。在此我们描述已知致畸化合物丙戊酸（VPA）对该系统的影响。
