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Development of a new test of developmental toxicology

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Research is being carried out in order to develop a test for toxicity of drugs on reproduction and development. The effect of drugs will be tested on cultures of eukaryotic cells as well as on gametes and entire embryos. The in vitro systems proposed have proven to be very sensitive to all tested drugs in the ranges which are considered therapeutic in human blood. Actually doxorubicin, phenytoin, valproic and retinoic acid clearly affect sea urchin morphogenesis; some of those drugs have already been tested on Drosophila development and were found to be toxic by a double approach (ie either by feeding them to the larvae and scoring the number of adults emerging or by injecting the adult females and observing the embryonic development of the corresponding oocytes). A good sensitivity has also been found when 2 drugs (doxorubicin and a gentamycin analogue) were added to cultures of the slime mould Dictyostelium discoideum and the number and volume of the cells were scored. In addition 1 strain of yeast was identified whose growth is particularly sensitive to the addition of phenytoin and doxorubicin. Finally human keratinocyte growth and differentiation in vitro was found to be affected by doxorubicin and phenytoin. To sum up, the results already obtained clearly indicate that the employed systems, alternatives to the traditional rodent embryos, are able to reveal the developmental toxicity of all the tested drugs, which are know to have some toxicity on humans.

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