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Using the social amoeba, Dictyosteliumdiscoideum, to screen agrochemicals fordevelopmental toxicity

Stanley, Madeleine

[Thesis]. Manchester, UK: The University of Manchester; 2016.

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Abstract

New agrochemicals must be carefully screened to make sure they have notoxic effects on development, as this can pose a danger to developing fetusesif their mother comes into contact with the compound. The current methodof screening new agrochemicals for developmental toxicity uses mammalianmodels, which is both expensive and time consuming. This project suggests aprocess that uses the social amoeba, Dictyostelium discoideum, to conduct pre-liminary screening of agrochemicals for developmental toxicity. The suitabilityof the first stages of the suggested process were tested using three fungicidescalled Corallo 1, Corallo 2 and Corallo 3. The effects these compounds haveon Dictyostelium cell growth was studied in axenic media and on SM agarplates in the presence of bacteria. The phenotypic effects of the drugs duringdevelopment were observed by growing Dictyostelium cells on agar to inducedevelopment. Both the growth experiment in media and the development ex-periment were also conducted using a mutant strain of Dictyostelium as a proofof principle experiment. Finally, optimisation experiments were carried outto improve the efficiency and quality of restriction enzyme-mediated integ-ration in preparation for screening the compounds against a mutant library.The growth experiments showed that the three compounds differed in potencyand that, whilst Corallo 2 was the most cytotoxic, Corallo 1 and 3 had theadditional effect of slowing proliferation. The development experiment clearlyshowed the differences and similarities between the phenotypes of the threecompounds, as well as highlighting the difference in potency the drugs hadduring growth and development. The mutant used in the proof of principleexperiment was found to be resistant to Corallo 3, but not Corallo 1 or 2, soscreening compounds against a mutant library in this manner could be usedto identify mutants of interest. The study highlighted areas of the suggestedpipeline that succeeded as well as areas for improvement. The clear phenotypesDictyostelium exhibited during these experiments showed that it is an ideal or-ganism to use for rapid preliminary screening. This new method of screeningnew agrochemicals for developmental toxicity could decrease the number ofunsuitable compounds that reach mammalian testing, saving both time andmoney.