Evaluation of the Teratogenic Potential of Valproic Acid Analogues in Transgenic Dictyostelium discoideum Strains

Toxicology in Vitro : an International Journal Published in Association with BIBRA
J TillnerT Dingermann

Abstract

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 ob...Continue Reading

References

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Citations

Jan 21, 2011·Analytical and Bioanalytical Chemistry·Neil F PascoRavi Gooneratne
May 17, 2002·Nature·Robin S B WilliamsAdrian J Harwood
Sep 4, 2008·American Journal of Veterinary Research·Courtney L FitzpatrickDietmar W Siemann
Aug 14, 2021·Toxicological Sciences : an Official Journal of the Society of Toxicology·Robert P BainesChristopher R L Thompson

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