Next Generation Testing Strategies for Assessment of Genotoxicity

项目摘要 众所周知，目前的遗传毒理学检测方法存在两个严重的缺陷。 首先，体外哺乳动物细胞基因毒性测试的吞吐能力较低，与当前的情况不符 需要。其次，传统的检测方法提供了简单的二元调用，遗传毒性或非遗传毒性。在这个方案中 很少或根本没有考虑效力，而且几乎没有提供关于分子靶标的信息。 和机械装置。这些危害特征方面的缺陷阻碍了遗传毒性数据的优化 为现代风险评估做出贡献，在现代风险评估中，这些信息至关重要。我们将解决这些主要问题 目前发展中的哺乳动物细胞遗传毒性体外检测方法存在的问题及相关 商业分析试剂盒显著提高了处理能力，并描述了遗传毒物的主要成分 分子靶标，同时提供有关效力的信息。曾经的生物标志物和一家 为此，已经开发了多重分析方法，将进行实验室间试验 用于评估方法可转移性的原型检测试剂盒。

Project Summary It is well recognized that current batteries of genetic toxicology assays exhibit two critical deficiencies. First, the throughput capacity of in vitro mammalian cell genotoxicity tests is low, and does not meet current needs. Second, conventional assays provide simplistic binary calls, genotoxic or non-genotoxic. In this scheme there is little or no consideration for potency, and virtually no information is provided about molecular targets and mechanisms. These deficiencies in hazard characterization prevent genotoxicity data from optimally contributing to modern risk assessments, where this information is essential. We will address these major problems with current in vitro mammalian cell genetic toxicity assays by developing methods and associated commercial assay kits that dramatically enhance throughput capacity, and delineate genotoxicants' primary molecular targets, while simultaneously providing information about potency. Once biomarkers and a family of multiplexed assays have been developed for these purposes, an interlaboratory trial will be performed with prototype assay kits to assess the transferability of the methods.