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Evaluation of the Teratogenic Potential of Valproic Acid Analogues in Transgenic Dictyostelium discoideum Strains.
MedLine Citation:
PMID:  20654429     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Very early during the development of new pharmaceuticals toxicological tests are most important. In addition to acute and chronic toxicity tests, it is crucial to estimate the teratogenic potential of promising drugs. We established a simple biological test system based on the cellular slime mold Dictyostelium discoideum. Under certain environmental conditions single cells of D. discoideum aggregate and undergo a relatively simple cell differentiation program, leading to the formation of stalk and spore cells. Transgenic D. discoideum strains carrying the bacterial beta-galactosidase gene under the control of various developmentally regulated D. discoideum promoters were shown to be useful tools to test the teratogenic potential of valproic acid (VPA). This study describes the effects of the VPA analogues S-4-yn-VPA, R-4-yn-VPA, and 2-ethyl-4-pentynoic acid on the D. discoideum developmental system. The presence of S-4-yn-VPA during D. discoideum development resulted in a strong inhibition of spore cell differentiation, whereas stalk cell formation was less affected. The enantiomer R-4-yn-VPA as well as 2-ethyl-4-pentynoic acid had only moderate effects on D. discoideum development. The above results are consistent with data obtained in mammalian teratogenicity assays, and suggest that D. discoideum development should be investigated with a number of additional substances to provide a simple alternative for high throughput screenings of new drugs.
Authors:
J Tillner; H Nau; T Winckler; T Dingermann
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  12     ISSN:  0887-2333     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  1998 Aug 
Date Detail:
Created Date:  2010-07-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  463-9     Citation Subset:  -    
Affiliation:
Institut fur Pharmazeutische Biologie, Universität Frankfurt/M. (Biozentrum), Marie-Curie-Strasse 9, D-60439 Frankfurt/M, Germany.
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