Benigni R, Giuliani A
Istituto Superiore di Sanità, Rome, Italy.
Environ Mol Mutagen. 1988;12(1):75-83. doi: 10.1002/em.2860120110.
This report puts into perspective a series of exploratory statistical analyses carried out on the major genotoxicity data bases. While large compilations of data, even though computerized, suffer from their own size and are quite intractable to scientific reflection and judgement, the multivariate data analysis methods used by us are specifically designed for reorganising the information in a rational way and highlighting the underlying regularities of the data. The analyses reported here refer to the following data bases: the International Program for the Evaluation of Short-Term Tests for Carcinogens, the International Program on Chemical Safety Collaborative Study on In Vitro Assays, the Gene-Tox data base, and a subset of the U.S. National Toxicology Program data. Although the various data bases consisted of different sets of chemicals and had different underlying rationales, a number of invariant associations among short-term test performances were highlighted. The overall evidence indicated that the traditional classification of assays (according to the criteria of genetic end-point and phylogenetic position of the assays) was in contrast with the actual, operational similarities among assay performances, in that the experimental responses of the tests to the large variety of chemicals under consideration pointed to an alternative classification scheme. This consisted of three major classes: 1) a class comprising the in vivo assays; 2) a class grouping together many of the most widely used in vitro assays (Salmonella, chromosomal aberrations, and sister chromatid exchanges in Chinese hamster ovary cells, the various mutation tests in mammalian cell systems, etc.); 3) a second in vitro assay class (with Syrian hamster embryo cell transformation, Saccharomyces cerevisiae XV185-14C, B. subtilis rec-, Escherichia coli pol A). Such classes had clearly differentiated features with respect to carcinogenicity prediction. The implications of these findings for the current debate on mutagenicity testing are discussed.
本报告全面介绍了对主要遗传毒性数据库进行的一系列探索性统计分析。尽管大量的数据汇编，即使是计算机化的，也因其自身规模而存在问题，并且很难进行科学思考和判断，但我们使用的多变量数据分析方法专门设计用于以合理的方式重组信息并突出数据的潜在规律。这里报告的分析涉及以下数据库：国际致癌物短期试验评估计划、国际化学品安全计划体外试验合作研究、基因毒性数据库以及美国国家毒理学计划数据的一个子集。尽管各个数据库由不同的化学物质集组成且有不同的基本原理，但短期试验性能之间的一些不变关联被凸显出来。总体证据表明，传统的试验分类（根据试验的遗传终点标准和系统发育位置）与试验性能之间实际的操作相似性形成对比，因为试验对所考虑的多种化学物质的实验反应指向了一种替代分类方案。该方案由三大类组成：1）包括体内试验的一类；2）将许多最广泛使用的体外试验归为一组的一类（沙门氏菌试验、染色体畸变试验以及中国仓鼠卵巢细胞中的姐妹染色单体交换试验、哺乳动物细胞系统中的各种突变试验等）；3）第二类体外试验（叙利亚仓鼠胚胎细胞转化试验、酿酒酵母XV185 - 14C试验、枯草芽孢杆菌rec - 试验、大肠杆菌pol A试验）。这些类别在致癌性预测方面具有明显不同的特征。讨论了这些发现对当前关于致突变性测试辩论的影响。
