Benigni R, Giuliani A
Laboratorio di Tossicologia Applicata, Istituto Superiore di Sanitá, Rome, Italy.
Mol Toxicol. 1987 Apr-Sep;1(2-3):143-66.
The main theme of this paper is to describe the basic requirements for assembling reliable batteries of short-term tests for carcinogenicity prediction. For this purpose, a subset of the data base generated by the International Program for Evaluation of Short-Term Tests for Carcinogens (IPESTTC) has been studied by different data-analysis methods. Much attention has been focused on the methodological dimensions of the problem, at the level of selection of both data and statistical techniques. Twenty-one of the most widely used short-term assays were considered. An exploratory study of the data base was first performed by factor analysis, showing similarities and dissimilarities between test performances and confirming our previous results obtained by cluster analysis. In this way the assays were divided into three groups on the basis of their responses to the chemicals. The Salmonella assay was in the central group, characterized by equilibrated performances in respect to sensitivity and specificity for carcinogens. Tests complementary to the Salmonella assay for sensitivity and specificity, respectively, were identified as well. A preliminary comparison of the IPESTTC results with the Gene-Tox data base is also presented. The test performances in respect to carcinogenicity prediction were then evaluated by discriminant analysis. When the subset of data was considered as a whole, the procedure resulted in a linear discriminant function able to correctly identify 84.2% of carcinogens and 83.3% of noncarcinogens. The correctly identified carcinogens summed to about 90% when adequate batteries of tests were used. This analysis yielded a number of observations. (1) Together with the selectivity indices (such as sensitivity and specificity), the operational complementarity between test performances must be ascertained and taken into account. (2) The batteries most effective at predicting carcinogenic activity were composed of three tests, one for each group. This finding converged with the fact that the three classes of assays were clearly differentiated for sensitivity and specificity, and in this sense were complementary to each other. (3) The performances of the batteries were not improved by adding more tests, but in several cases the opposite effect occurred. (4) Estimation of the probability of the chemicals of being carcinogenic, starting from qualitative genotoxicity data, is possible.
本文的主题是描述组装用于致癌性预测的可靠短期测试电池的基本要求。为此，国际短期致癌物测试评估计划（IPESTTC）生成的数据库子集已通过不同的数据分析方法进行了研究。问题的方法层面，即在数据和统计技术的选择层面，受到了很多关注。考虑了21种最广泛使用的短期检测方法。首先通过因子分析对数据库进行了探索性研究，显示了测试性能之间的异同，并证实了我们之前通过聚类分析获得的结果。通过这种方式，根据检测方法对化学物质的反应将其分为三组。沙门氏菌检测在中间组，其特点是对致癌物的敏感性和特异性表现平衡。还确定了分别对沙门氏菌检测的敏感性和特异性具有互补性的检测方法。还给出了IPESTTC结果与基因毒性数据库的初步比较。然后通过判别分析评估检测方法在致癌性预测方面的性能。当将数据子集作为一个整体考虑时，该过程产生了一个线性判别函数，能够正确识别84.2%的致癌物和83.3%的非致癌物。当使用适当的测试电池时，正确识别的致癌物总计约为90%。该分析得出了一些观察结果。（1）除了选择性指标（如敏感性和特异性）外，还必须确定并考虑测试性能之间的操作互补性。（2）预测致癌活性最有效的测试电池由三项测试组成，每组一项。这一发现与以下事实相符，即这三类检测方法在敏感性和特异性方面有明显差异，从这个意义上说，它们相互补充。（3）增加更多测试并没有提高测试电池的性能，在几种情况下反而产生了相反的效果。（4）从定性的遗传毒性数据出发，有可能估计化学物质致癌的概率。
