A database of 91 chemicals with published data from both transgenic rodent mutation (TGR) and rodent comet assays has been compiled. The objective was to compare the sensitivity of the two assays for detecting genotoxicity. Critical aspects of study design and results were tabulated for each dataset. There were fewer datasets from rats than mice, particularly for the TGR assay, and therefore, results from both species were combined for further analysis. TGR and comet responses were compared in liver and bone marrow (the most commonly studied tissues), and in stomach and colon evaluated either separately or in combination with other GI tract segments. Overall positive, negative, or equivocal test results were assessed for each chemical across the tissues examined in the TGR and comet assays using two approaches: 1) overall calls based on weight of evidence (WoE) and expert judgement, and 2) curation of the data based on a priori acceptability criteria prior to deriving final tissue specific calls. Since the database contains a high prevalence of positive results, overall agreement between the assays was determined using statistics adjusted for prevalence (using AC1 and PABAK). These coefficients showed fair or moderate to good agreement for liver and the GI tract (predominantly stomach and colon data) using WoE, reduced agreement for stomach and colon evaluated separately using data curation, and poor or no agreement for bone marrow using both the WoE and data curation approaches. Confidence in these results is higher for liver than for the other tissues, for which there were less data. Our analysis finds that comet and TGR generally identify the same compounds (mainly potent mutagens) as genotoxic in liver, stomach and colon, but not in bone marrow. However, the current database content precluded drawing assay concordance conclusions for weak mutagens and non-DNA reactive chemicals.

中文翻译：

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转基因啮齿动物突变与体内91种化学物质的彗星分析反应的比较。

已建立了91种化学物质的数据库，其中已公开了转基因啮齿动物突变（TGR）和啮齿动物彗星试验的数据。目的是比较两种测定法检测基因毒性的敏感性。将每个数据集的研究设计和结果的关键方面制成表格。来自大鼠的数据集少于小鼠，尤其是用于TGR分析的数据集，因此，将两种物种的结果合并以进行进一步分析。在肝脏和骨髓（最常研究的组织）中比较了TGR和彗星反应，并在胃和结肠中分别或结合其他胃肠道片段进行了评估。使用以下两种方法评估了在TGR和彗星试验中检查的组织中每种化学物质的总体阳性，阴性或模棱两可的测试结果：1）基于证据权重（WoE）和专家判断的总体调用，以及2）在得出最终组织特定调用之前，基于先验可接受标准对数据进行整理。由于数据库中阳性结果的患病率很高，因此使用针对患病率进行调整的统计数据（使用AC1和PABAK）确定了测定之间的总体一致性。这些系数显示，使用WoE对肝脏和胃肠道（主要是胃和结肠数据）的一致性达到中度或中度至良好，使用数据处理分别评估的胃和结肠对一致性的降低，或者使用WoE和数据管理方法。肝脏对这些结果的信心要高于其他组织（数据较少）。我们的分析发现，彗星和TGR通常在肝，胃和结肠中鉴定出相同的化合物（主要是有效的诱变剂）作为遗传毒性，但在骨髓中却没有。但是，当前的数据库内容排除了弱诱变剂和非DNA反应性化学物质的绘图分析一致性结论。