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将果蝇胚胎细胞培养物用作体外致畸试验。

Use of Drosophila embryo cell cultures as an in vitro teratogen assay.

作者信息

Bournias-Vardiabasis N, Teplitz R L

出版信息

Teratog Carcinog Mutagen. 1982;2(3-4):333-41. doi: 10.1002/1520-6866(1990)2:3/4<333::aid-tcm1770020315>3.0.co;2-y.

Abstract

An in vitro assay has been developed for detecting teratogens by adding them to primary cultures of embryonic Drosophila cells and analyzing the degree of change in cell differentiation and tissue formation. Cultures are scored by an automated image analysis system that counts the number of myotubes and ganglia in culture. A decrease in their number compared to controls is taken as an indication of teratogenicity. In the group of 100 drugs and chemicals examined thus far in this assay, a high correlation with known teratogenic activity has been obtained with few false-positives or false-negatives. Procedures also have been developed for testing metabolic products of ingested compounds for teratogenicity. Mice and rats are fed the particular agent to be tested, and their serum is then added to the differentiating culture. Preliminary trials with human serum from patients receiving chemotherapy have also been performed. With further testing, validation, and incorporation of a metabolic activation system, it is hoped that this assay can be used, along with a battery of other in vitro assays, as a screen for the large number of agents awaiting comprehensive testing of their teratogenic potential. We also see the use of this assay as means to gain further information on the basic biochemical and developmental aspects of teratogenesis.

摘要

已开发出一种体外检测方法,通过将致畸剂添加到胚胎果蝇细胞的原代培养物中,并分析细胞分化和组织形成的变化程度来检测致畸剂。培养物由自动图像分析系统进行评分,该系统会对培养物中的肌管和神经节数量进行计数。与对照组相比,它们的数量减少被视为致畸性的指标。在该检测方法迄今为止检测的100种药物和化学物质中,与已知致畸活性具有高度相关性,假阳性或假阴性很少。还开发了检测摄入化合物代谢产物致畸性的程序。给小鼠和大鼠喂食待检测的特定试剂,然后将它们的血清添加到正在分化的培养物中。也已对接受化疗患者的人血清进行了初步试验。通过进一步测试、验证并纳入代谢激活系统,希望该检测方法能够与一系列其他体外检测方法一起,用于筛查大量有待全面检测其致畸潜力的试剂。我们还认为该检测方法可作为获取致畸发生基本生化和发育方面更多信息的手段。

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