Environment and Health Department, Istituto Superiore di Sanita', 00161 Rome, Italy.
Mutagenesis. 2012 Jan;27(1):87-92. doi: 10.1093/mutage/ger064. Epub 2011 Sep 30.
This paper presents a new curated database on in vivo micronucleus mutagenicity results, called ISSMIC. It is freely available at: http://www.iss.it/ampp/dati/cont.php?id=233&lang=1&tipo=7. The experimental results were critically reviewed, and evidence on target cell exposure was considered as well. The inspection of ISSMIC demonstrates that a large proportion of reported negative results in the literature (231 out 566 ISSMIC chemicals) lack a clear-cut, direct demonstration of toxicity at the target cells. Using this updated database, the predictive value of a compilation of Structural Alerts (SA) for in vivo micronucleus recently implemented in the expert system Toxtree was investigated. Individually, most of the SA showed a high Positive Predictivity (∼80%), but the need for further expanding the list of alerts was pointed out as well. The role of in vivo micronucleus in strategies for carcinogenicity prediction was re-evaluated. In agreement with previous analyses, the data point to a low overall correlation with carcinogenicity. In addition, given the cost in animal lives and the time required for the experimentation, in many programs, the in vivo tests are used only to assess in vitro positive results. The ability of in vivo micronucleus to identify real positives (i.e. carcinogens) among chemicals positive in Salmonella or among chemicals inducing in vitro chromosomal aberrations was studied. It appears that the in vivo micronucleus test does not have added value and rather impairs the prediction ability of the in vitro tests alone. The overall evidence indicates that in vivo micronucleus--in its present form--cannot be considered an useful tool for routine genotoxicity testing but should be used in targeted mechanistic studies.
本文提出了一个新的体内微核诱变性研究的精心整理的数据库，称为 ISSMIC。它可在以下网址免费获取：http://www.iss.it/ampp/dati/cont.php?id=233&lang=1&tipo=7。实验结果经过了严格的审查，并考虑了靶细胞暴露的证据。对 ISSMIC 的检查表明，文献中报告的大量阴性结果（ISSMIC 化学物质 566 种中有 231 种）缺乏对靶细胞毒性的明确直接证明。使用这个更新的数据库，研究了最近在专家系统 Toxtree 中实现的结构警报（SA）对体内微核的预测价值的编译。单独使用时，大多数 SA 显示出较高的阳性预测率（约 80%），但也指出需要进一步扩展警报列表。体内微核在致癌性预测策略中的作用也进行了重新评估。与之前的分析一致，数据表明与致癌性的总体相关性较低。此外，考虑到动物生命的成本和实验所需的时间，在许多计划中，体内试验仅用于评估体外阳性结果。研究了体内微核识别真阳性（即致癌剂）的能力，即阳性的沙门氏菌或引起体外染色体畸变的化学物质。似乎体内微核试验没有附加值，反而会损害单独进行的体外试验的预测能力。总体证据表明，目前形式的体内微核不能被视为常规遗传毒性测试的有用工具，而应在有针对性的机制研究中使用。
