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癌基因组学项目:基于组学的体外致癌性筛选试验开发中模型化合物的关键选择

The carcinoGENOMICS project: critical selection of model compounds for the development of omics-based in vitro carcinogenicity screening assays.

作者信息

Vinken Mathieu, Doktorova Tatyana, Ellinger-Ziegelbauer Heidrun, Ahr Hans-Jürgen, Lock Edward, Carmichael Paul, Roggen Erwin, van Delft Joost, Kleinjans Jos, Castell José, Bort Roque, Donato Teresa, Ryan Michael, Corvi Raffaella, Keun Hector, Ebbels Timothy, Athersuch Toby, Sansone Susanna-Assunta, Rocca-Serra Philippe, Stierum Rob, Jennings Paul, Pfaller Walter, Gmuender Hans, Vanhaecke Tamara, Rogiers Vera

机构信息

Department of Toxicology, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, B-1090 Brussels, Belgium.

出版信息

Mutat Res. 2008 Sep-Oct;659(3):202-10. doi: 10.1016/j.mrrev.2008.04.006. Epub 2008 Apr 26.

Abstract

Recent changes in the European legislation of chemical-related substances have forced the scientific community to speed up the search for alternative methods that could partly or fully replace animal experimentation. The Sixth Framework Program project carcinoGENOMICS was specifically raised to develop omics-based in vitro screens for testing the carcinogenic potential of chemical compounds in a pan-European context. This paper provides an in-depth analysis of the complexity of choosing suitable reference compounds used for creating and fine-tuning the in vitro carcinogenicity assays. First, a number of solid criteria for the selection of the model compounds are defined. Secondly, the strategy followed, including resources consulted, is described and the selected compounds are briefly illustrated. Finally, limitations and problems encountered during the selection procedure are discussed. Since selecting an appropriate set of chemicals is a frequent impediment in the early stages of similar research projects, the information provided in this paper might be extremely valuable.

摘要

欧洲有关化学相关物质的立法近期发生的变化,迫使科学界加快寻找能够部分或完全替代动物实验的替代方法。第六框架计划项目“癌基因学”(carcinoGENOMICS)专门提出要在泛欧洲背景下开发基于组学的体外筛选方法,用于测试化合物的致癌潜力。本文深入分析了选择用于创建和微调体外致癌性检测的合适参考化合物的复杂性。首先,定义了一些选择模型化合物的可靠标准。其次,描述了所遵循的策略,包括参考的资源,并简要说明了所选化合物。最后,讨论了选择过程中遇到的限制和问题。由于选择一组合适的化学物质在类似研究项目的早期阶段常常是一个障碍,本文提供的信息可能极具价值。

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