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使用推荐的细胞毒性指数对体外染色体畸变试验中过去呈阳性的化学物质进行回顾性评估的必要性。

Necessity for retrospective evaluation of past-positive chemicals in in vitro chromosomal aberration tests using recommended cytotoxicity indices.

作者信息

Honda Hiroshi, Fujita Yurika, Kasamatsu Toshio, Fuchs Anne, Fautz Rolf, Morita Osamu

机构信息

R&D Safety Science Research, Kao Corporation, 2606 Akabane, Ichikai-Machi, Haga-Gun, Tochigi, 321-3497 Japan.

Kao Europe Research Laboratories, Kao Germany GmbH, Darmstadt, 64297 Germany.

出版信息

Genes Environ. 2018 Jan 10;40:2. doi: 10.1186/s41021-017-0091-y. eCollection 2018.

Abstract

We have demonstrated that retrospective evaluation of existing data of in vitro chromosomal aberration test using the new cytotoxicity indices RICC (relative increase in cell count) or RPD (relative population doubling) reduces the false-positive rate. We have constructed an algorithm to predict the likelihood that past-positive results would differ when retested accordingly. Here, we emphasize the importance of reviewing existing in vitro chromosomal aberration test results. The present Letter not only supports the rediscovery of potentially useful chemicals excluded from further development as a result of misclassification due to in vitro false-positive results, but also contributes to the development of a precise Quantitative Structure-Activity Relationship (QSAR) model by providing an appropriate training data-set. Furthermore, re-evaluation is expected to provide novel insights into underlying mechanisms and/or key structures involved in the development of chromosomal aberrations.

摘要

我们已经证明,使用新的细胞毒性指数RICC(细胞计数相对增加)或RPD(相对群体倍增)对体外染色体畸变试验的现有数据进行回顾性评估可降低假阳性率。我们构建了一种算法,以预测过去的阳性结果在重新测试时出现差异的可能性。在此,我们强调审查现有体外染色体畸变试验结果的重要性。本信函不仅支持重新发现因体外假阳性结果导致错误分类而被排除在进一步开发之外的潜在有用化学品,还通过提供合适的训练数据集有助于精确的定量构效关系(QSAR)模型的开发。此外,重新评估有望为染色体畸变发展所涉及的潜在机制和/或关键结构提供新的见解。

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Chromothripsis from DNA damage in micronuclei.微核中DNA损伤导致的染色体碎裂
Nature. 2015 Jun 11;522(7555):179-84. doi: 10.1038/nature14493. Epub 2015 May 27.

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