de Serres F J, Malling H V, Brockman H E, Ong T M
Laboratory of Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709-2233, USA.
Mutat Res. 1997 Apr 14;375(1):53-72. doi: 10.1016/s0027-5107(96)00254-0.
The data from forward-mutation experiments to obtain specific-locus mutations at two closely linked loci in the adenine-3 (ad-3) region of heterokaryon 12 (H-12) of Neurospora crassa have been tabulated to determine the relative frequencies and mutational spectra of ad-3 mutants occurring spontaneously and those induced by 22 different chemical treatments. Previous studies have demonstrated that specific-locus mutations at these two loci result from 5 major genotypic classes, namely two classes of gene/point mutations (ad-3AR and ad-3BR), and 3 classes of multilocus deletion mutations ([ad-3A]IR, [ad-3B]IR and [ad-3A ad-3B]IR). In addition, prior studies have demonstrated that some chemical mutagens induced ad-3 mutants exclusively, or almost exclusively, by gene/point mutation and other chemical mutagens by gene/point mutation and multilocus deletion mutation. In the latter cases, there was wide variation in the percentages of ad-3 mutants in these 5 major genotypic classes. Two comparative methods of analysis that also were used to compare spontaneous and chemical-induced ad-3 mutational spectra included X2-tests on the numbers of ad-3 mutants resulting in the following two sets of ratios: (1) gene/point mutations and multilocus deletion mutations; and (2) complementing and non-complementing ad-3BR, mutants. Combination of the p-values from X2-tests for these two methods of comparison demonstrated that all 22 chemicals induce a spectrum of ad-3 mutants that is qualitatively different from that occurring spontaneously. In addition, these same two methods of comparison have been used to compare the mutagenic effects of each of the 22 chemical treatments with each other. Combination of the data from these two methods of comparison has demonstrated that 93.1% (215/231) of the pairwise combinations of these 22 chemicals were different from each other. The implication of these experimental data on the induction of specific-locus mutations in somatic cells of Neurospora for genetic risk assessment exercises is discussed.
已将来自正向突变实验的数据制成表格，这些实验旨在获得粗糙脉孢菌异核体12（H - 12）腺嘌呤 - 3（ad - 3）区域中两个紧密连锁位点的特定位点突变，以确定自发产生的ad - 3突变体以及由22种不同化学处理诱导产生的ad - 3突变体的相对频率和突变谱。先前的研究表明，这两个位点的特定位点突变来自5种主要的基因型类别，即两类基因/点突变（ad - 3AR和ad - 3BR），以及3类多位点缺失突变（[ad - 3A]IR、[ad - 3B]IR和[ad - 3A ad - 3B]IR）。此外，先前的研究表明，一些化学诱变剂仅通过基因/点突变诱导ad - 3突变体，或几乎仅通过基因/点突变诱导，而其他化学诱变剂则通过基因/点突变和多位点缺失突变诱导。在后一种情况下，这5种主要基因型类别中ad - 3突变体的百分比存在很大差异。用于比较自发和化学诱导的ad - 3突变谱的两种比较分析方法包括对导致以下两组比率的ad - 3突变体数量进行卡方检验：（1）基因/点突变和多位点缺失突变；（2）互补和非互补的ad - 3BR突变体。这两种比较方法的卡方检验p值相结合表明，所有22种化学物质诱导的ad - 3突变体谱在质量上与自发产生的不同。此外，这两种相同的比较方法已用于比较22种化学处理中每种处理之间的诱变效果。这两种比较方法的数据相结合表明，这22种化学物质的成对组合中有93.1%（215/231）彼此不同。讨论了这些实验数据对粗糙脉孢菌体细胞中特定位点突变诱导进行遗传风险评估的意义。
