Drosophotoxicology: the growing potential for Drosophila in neurotoxicology.
Drosophotoxicology: the growing potential for Drosophila in neurotoxicology.
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DOI：
10.1016/j.ntt.2009.06.004
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发表时间：
2010-01
影响因子：
2.9
通讯作者：
Rand, Matthew D.
中科院分区：
文献类型：
--
作者：
Rand, Matthew D.
关键词：
了解神经毒性机制是破译正在发育或成熟的神经系统中的哪些基因和基因产物是我们在环境中遇到的化学物质破坏的目标的挑战。我们对神经系统发育和生理学的了解非常先进，这在很大程度上是因为在简单的非哺乳动物模型中进行的研究。目前商业使用的80,000多种化学物质缺乏毒理学数据，每年大约有2,000种新化学物质推出，这使得开发敏感和快速的分析方法来筛选神经毒性至关重要。在这篇文章中，我提倡在现代毒理学测试中使用果蝇，强调它在分析神经发育和行为方面的独特属性。综述了果蝇模型的特点，并提出了其在毒理学中应用的总体方案。还突出了苍蝇在评估我们环境中的常见毒物方面卓有成效的例子。Fly模型的开发和应用可能对毒理学最有好处的三个领域：1)优化敏感终点以进行路径特异性筛选，2)适应高通量要求的化学毒物文库分析，3)优化遗传和分子方案以更快地识别毒物与基因的相互作用。虽然果蝇模型存在缺陷，将其排除在有效的毒理学测试之外，但在某些领域，果蝇和人之间的基本细胞和发育机制的保守性足够广泛，足以保证果蝇模型在今天的毒理学测试中发挥核心作用。
Understanding neurotoxic mechanisms is a challenge of deciphering which genes and gene products in the developing or mature nervous system are targeted for disruption by chemicals we encounter in our environment. Our understanding of nervous system development and physiology is highly advanced due in large part to studies conducted in simple non-mammalian models. The paucity of toxicological data for the more than 80,000 chemicals in commercial use today, and the approximately 2,000 new chemicals introduced each year, make development of sensitive and rapid assays to screen for neurotoxicity paramount. In this article I advocate the use of Drosophila in the modern regimen of toxicological testing, emphasizing its unique attributes for assaying neurodevelopment and behavior. Features of the Drosophila model are reviewed and a generalized overall scheme for its use in toxicology is presented. Examples of where the fly has proven fruitful in evaluating common toxicants in our environment are also highlighted. Attention is drawn to three areas where development and application of the fly model might benefit toxicology the most: 1) optimizing sensitive endpoints for pathway-specific screening, 2) accommodating high throughput demands for analysis of chemical toxicant libraries, 3) optimizing genetic and molecular protocols for more rapid identification toxicant-by-gene interactions. While there are shortcomings in the Drosophila model, which exclude it from effective toxicological testing it certain arenas, conservation of fundamental cellular and developmental mechanisms between flies and man are extensive enough to warrant a central role for the Drosophila model in toxicological testing of today.
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影响因子：
56.9
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