کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5859325 | 1132469 | 2013 | 13 صفحه PDF | دانلود رایگان |

As the developing brain is exquisitely vulnerable to chemical disturbances, testing for developmental neurotoxicity of a substance is an important aspect of characterizing its tissue specific toxicity. Mouse embryonic stem cells (mESCs) can be differentiated toward a neural phenotype, and this can be used as a model for early brain development. We developed a new in vitro assay using mESCs to predict adverse effects of chemicals and other compounds on neural development - the so-called DNT-EST. After treatment of differentiating stem cells for 48Â h or 72Â h, at two key developmental stages endpoint for neural differentiation, viability, and proliferation were assessed. As a reference, we similarly treated undifferentiated stem cells 2 days after plating for 48Â h or 72Â h in parallel to the differentiating stem cells. Here, we show that chemical testing of a training set comprising nine substances (six substances of known developmental toxicity and three without specific developmental neurotoxicity) enabled a mathematical prediction model to be formulated that provided 100% predictivity and accuracy for the given substances, including in leave-one-out cross-validation. The described test method can be performed within two weeks, including data analysis, and provides a prediction of the developmental neurotoxicity potency of a substance.
Journal: Toxicology - Volume 314, Issue 1, 6 December 2013, Pages 135-147