Caspary W J, Daston D S, Myhr B C, Mitchell A D, Rudd C J, Lee P S
Cellular and Genetic Toxicology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
Environ Mol Mutagen. 1988;12 Suppl 13:195-229. doi: 10.1002/em.2860120506.
The L5178Y mouse lymphoma cell mutagenesis assay is used to detect the mutagenic activity of chemicals in a mammalian cell system. To evaluate this assay we compared the results of assays performed independently on 63 chemicals by laboratories at SRI International and Litton Bionetics, Inc. The two laboratories used similar protocols. The solvent and positive control mutant frequencies and cloning efficiencies obtained by the two laboratories were similar, which justified the use of the same quality-control criteria and analytical procedures for analyzing the results from both laboratories. The rate of concordance between the two laboratories was 92% for tests in the absence of S9 activation and 95% for tests in its presence. The results of the assays agreed for 57 of the 63 chemicals; three chemicals could not be compared because there were questionable calls in at least one of the laboratories; the results disagreed for the three remaining chemicals. The concordance rate for these overall assay evaluations was 95%. The interlaboratory concordance rates were similar to concordance rates for replicate experiments within the laboratories (96% at LBI, 94% at SRI). The mouse lymphoma cell mutagenicity results are concordant with the rodent chronic assay results in 78% of 50 chemicals and with the Salmonella assay results in 79% of 56 chemicals. Fifteen carcinogens were examined for genotoxic effects in mouse lymphoma, Salmonella, Chinese hamster ovary (CHO) chromosomal aberration, and CHO sister chromatid exchange assay. Eight of these were positive in all four assays. Of the seven noncarcinogens that were tested in these four assays, none was negative in all four. The main conclusion to be drawn from this study is that the mouse lymphoma cell forward mutation assay, as performed and evaluated in this study, detects chemical mutagenicity in a manner that is highly consistent with other genetic endpoints as well as rodent carcinogenicity studies. Thus the assay quality control and response criteria established in this study led not only to a high degree of reproducibility but also to an apparently reliable detection of mutagenic activity.
L5178Y小鼠淋巴瘤细胞诱变试验用于检测化学物质在哺乳动物细胞系统中的诱变活性。为评估该试验，我们比较了SRI国际公司和Litton Bionetics公司的实验室分别对63种化学物质独立进行试验的结果。两个实验室使用了相似的方案。两个实验室获得的溶剂和阳性对照突变频率以及克隆效率相似，这证明对两个实验室的结果采用相同的质量控制标准和分析程序是合理的。在无S9激活的试验中，两个实验室的一致性率为92%；在有S9激活的试验中，一致性率为95%。63种化学物质中有57种试验结果一致；三种化学物质无法比较，因为至少有一个实验室的结果存在疑问；其余三种化学物质的结果不一致。这些总体试验评估的一致性率为95%。实验室间的一致性率与各实验室内重复实验的一致性率相似（LBI为96%，SRI为94%）。50种化学物质中有78%的小鼠淋巴瘤细胞诱变性结果与啮齿动物慢性试验结果一致，56种化学物质中有79%的结果与沙门氏菌试验结果一致。对15种致癌物进行了小鼠淋巴瘤、沙门氏菌、中国仓鼠卵巢（CHO）染色体畸变和CHO姐妹染色单体交换试验的遗传毒性效应检测。其中8种在所有四项试验中均呈阳性。在这四项试验中检测的7种非致癌物中，没有一种在所有四项试验中均为阴性。本研究得出的主要结论是，本研究中进行和评估的小鼠淋巴瘤细胞正向突变试验检测化学诱变性的方式与其他遗传终点以及啮齿动物致癌性研究高度一致。因此，本研究中建立的试验质量控制和反应标准不仅导致了高度的可重复性，而且对诱变活性的检测显然可靠。
