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短期检测评估的合理方法:同质数据库分析

Rational approach to the evaluation of short-term tests: analysis of a homogeneous data base.

作者信息

Benigni R, Giuliani A

出版信息

J Toxicol Environ Health. 1985;16(3-4):333-53. doi: 10.1080/15287398509530746.

DOI:10.1080/15287398509530746
PMID:4087307
Abstract

The major thrust in this study is the analysis by mathematical classification techniques of a homogeneous set of data on short-term tests. The data base generated by the International Program for the Evaluation of Short-Term Tests for Carcinogens was chosen as the model system and was studied first by cluster analysis. For this purpose, an adequate subset of data was selected and the associations between tests were explored on the basis of their performances over a range of chemicals. Then the complementary analysis of the functional relationships between the chemicals, in respect to their genotoxic effects, was performed. In both cases, a clearly structured underlying typology was brought out. Specific indications were suggested by this analysis. First, the data base studied indicated a relative independence of the performances of the assays from phylogeny and genetic endpoints. Second, the chemicals assayed were grouped together (on the basis of functional similarities) according to relationships that may represent a ground for structure-activity relationship investigations. A further important topic of this study was the quantitative evaluation of the test performances in respect to carcinogenicity prediction. To assess the effectiveness with which short-term assays can detect carcinogens and noncarcinogens, discriminant-analysis techniques were applied. On the data set considered here, the short-term tests showed 83.9% global ability to correctly classify chemicals as carcinogens or noncarcinogens. Even if these results are directly dependent on the representativity of the data set chosen, they clearly point out to the high heuristic potency of applying data-analysis techniques to genetic toxicology research.

摘要

本研究的主要重点是通过数学分类技术对一组关于短期试验的同类数据进行分析。由国际致癌物短期试验评估计划生成的数据库被选为模型系统,并首先通过聚类分析进行研究。为此,选择了足够的数据子集,并根据它们在一系列化学物质上的表现来探索试验之间的关联。然后,针对化学物质的遗传毒性效应,对它们之间的功能关系进行了补充分析。在这两种情况下,都揭示了一种结构清晰的潜在类型学。该分析提出了具体的指示。首先,所研究的数据库表明,这些检测方法的性能相对独立于系统发育和遗传终点。其次,根据可能代表结构 - 活性关系研究基础的关系,将所检测的化学物质(基于功能相似性)分组。本研究的另一个重要主题是对致癌性预测方面的检测性能进行定量评估。为了评估短期试验检测致癌物和非致癌物的有效性,应用了判别分析技术。在此处考虑的数据集上,短期试验显示出将化学物质正确分类为致癌物或非致癌物的整体能力为83.9%。即使这些结果直接取决于所选数据集的代表性,但它们清楚地表明了将数据分析技术应用于遗传毒理学研究的高度启发式效力。

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