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Toxicogenomics: In Vivo vs In Vitro Mammalian Model Systems

机译:毒物学:在体外哺乳动物模型系统中的体内VS

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When new remediation technologies are developed, it is critical to verify not only the disappearance of the parent compound, but the appearance of any intermediates or end products. The potential toxicity of the intermediates and end products should be assessed to ensure that the remediation process is not creating a different hazard once the parent compound is destroyed. Current assessment techniques for predicted intermediates and end products can prove costly and time consuming. Rapid screening methodologies such as MicroTox? can provide some information, but the results from screening assays based on bacterial responses may not extrapolate well to mammalian systems. In vivo exposures typically require large quantities of the test compound, and typically there is limited availability of standards for the intermediates and end products. We are investigating the potential of mammalian primary and stem cell cultures in conjunction with gene expression analysis for understanding the mechanisms of toxicity. If successful, this technology' could be applied to compounds of unknown toxicological properties (such as remediation intermediates and end products), in a manner similar to that being used in the pharmaceutical field where gene expression profiles from whole animal exposures are being used to understand mechanisms of toxicity.
机译:当开发新的修复技术时,不仅验证母体化合物的消失,而且是任何中间体或最终产品的外观至关重要。应评估中间体和最终产品的潜在毒性,以确保在母体化合物被破坏后,修复过程没有产生不同的危害。目前预测中间体和最终产品的评估技术可以证明昂贵且耗时。快速筛选方法,如Microtox?可以提供一些信息,但是基于细菌反应的筛选测定结果可能不会易于哺乳动物系统。在体内曝光中通常需要大量的测试化合物,并且通常有限可用性的中间体和最终产品的可用性。我们正在研究哺乳动物初级和干细胞培养的潜力与理解毒性机制的基因表达分析。如果成功,这种技术可以应用于未知毒理学性质(例如修复中间体和最终产品)的化合物,以类似于用于从整个动物曝光的基因表达谱的基因表达谱所理解的药物领域的方式毒性机制。

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