Russell L B, Selby P B, von Halle E, Sheridan W, Valcovic L
Mutat Res. 1981 May;86(3):329-54. doi: 10.1016/0165-1110(81)90010-5.
The mouse specific-locus test with visible markers (SLT) has been the only extensively used method for detecting and quantifying the induction of heritable point mutations (intragenic changes and small deficiencies) in mammals. Mutations are detected in first-generation offspring; and scoring is simple, objective, and rapid. Different germ-cell stages can be sampled, including those of greatest pertinence for genetic risk assessment. The differential probability of involving the various loci of the marked set makes the method capable of detecting qualitative (as well as quantitative) differences between the actions of mutagens. Control SLT frequencies for males reported by 4 sets of investigators are in excellent agreement and were summed as a "historical control" (801406 observations) for use in our calculations. Experimental results were classified as positive, negative, or inconclusive based upon a multiple-decision procedure produced by the testing of the following 2 hypotheses: (1) the mutation frequency (induced + spontaneous) of treated mice is not higher than the spontaneous mutation frequency, and (2) the induced mutation frequency of treated mice is no less than 4 times the historical-control mutation frequency. Each hypothesis was tested at the 5% significance level. Because of the low mutation frequency in a very large control, the SLT is capable of yielding positive results in relatively small samples. We reviewed 58 publications, SLT results have been reported for 25 chemical agents, of which 17 (representing 21 chemical classes) gave results that were positive or negative by our criteria. The frequency of positive agents was 6 of 14, 5 of 5, and 0 of 1 conclusively tested, respectively, in spermatogonia, post-spermatogonial stages, and unspecified male germ cells. Depending on the chemical used, post-spermatogonial stages can be of greater, less, or equal sensitivity relative to spermatogonia. The SLT was strongly positive for some chemicals that are not mutagenic (or only weakly so) in lower systems, and there are several examples of the reverse situation. Factors which presumably operated to cause these differences (e.g., metabolism, transport, repair in germ cells) are likely also to operate for transmitted point mutations in man.
带有可见标记的小鼠特定位点试验（SLT）一直是检测和定量哺乳动物中可遗传点突变（基因内变化和小缺失）诱导作用的唯一广泛使用的方法。在第一代后代中检测突变；评分简单、客观且快速。可以对不同的生殖细胞阶段进行采样，包括那些对遗传风险评估最具相关性的阶段。涉及标记组各个位点的不同概率使得该方法能够检测诱变剂作用之间的定性（以及定量）差异。4组研究人员报告的雄性对照SLT频率非常一致，并汇总为“历史对照”（801406次观察）用于我们的计算。根据对以下两个假设进行测试产生的多重决策程序将实验结果分类为阳性、阴性或无结论：（1）处理过的小鼠的突变频率（诱导+自发）不高于自发突变频率，以及（2）处理过的小鼠的诱导突变频率不少于历史对照突变频率的4倍。每个假设都在5%的显著性水平上进行测试。由于在非常大的对照中突变频率较低，SLT能够在相对较小的样本中产生阳性结果。我们查阅了58篇出版物，已报告了25种化学试剂的SLT结果，其中17种（代表21个化学类别）根据我们的标准给出了阳性或阴性结果。在精原细胞、精原细胞后阶段和未指定的雄性生殖细胞中，分别有14种中的6种、5种中的5种和1种中的0种经最终测试为阳性试剂。根据所使用的化学物质，精原细胞后阶段相对于精原细胞的敏感性可能更高、更低或相等。对于一些在较低系统中无诱变作用（或只有微弱诱变作用）的化学物质，SLT呈强阳性，也有几例相反的情况。可能导致这些差异的因素（例如，生殖细胞中的代谢、转运、修复）也可能对人类中的传递性点突变起作用。
