Penman B W, Crespi C L
Gentest Corporation, Woburn, MA 01801.
Environ Mol Mutagen. 1987;10(1):35-60. doi: 10.1002/em.2850100106.
We describe here historical negative control data bases for gene locus mutation assays at the thymidine kinase locus and hypoxanthine-guanine phosphoribosyl transferase locus in TK6 and AHH-1 human lymphoblasts, respectively. Protocols have been designed which minimize the variability among independent experiments and thus facilitate the use of historical negative control data bases for assay analysis. The historical negative control data bases for both cell lines can be accurately modeled as gamma or Poisson distributions; confidence limits can be calculated from these distributions. We describe and justify a mutagenicity assay analysis procedure which uses a comparison to the concurrent negative control cultures via a t-test in conjunction with a comparison to the historical negative control data base. The incorporation of a comparison to the historical negative control data base allows the use of a higher confidence level without substantially sacrificing the sensitivity of the mutation assays. The analysis of the mutagenicity of saccharin in TK6 cells is presented as an example; saccharin was found to be nonmutagenic under the conditions tested.
我们在此分别描述了TK6和AHH-1人淋巴母细胞中胸苷激酶基因座和次黄嘌呤-鸟嘌呤磷酸核糖基转移酶基因座基因位点突变试验的历史阴性对照数据库。已设计出方案，可最大程度减少独立实验之间的变异性，从而便于使用历史阴性对照数据库进行试验分析。两种细胞系的历史阴性对照数据库均可准确建模为伽马分布或泊松分布；可从这些分布计算置信限。我们描述并论证了一种致突变性试验分析程序，该程序通过t检验与同期阴性对照培养物进行比较，并与历史阴性对照数据库进行比较。与历史阴性对照数据库进行比较，可在不大幅牺牲突变试验灵敏度的情况下使用更高的置信水平。以糖精在TK6细胞中的致突变性分析为例；发现在测试条件下糖精无致突变性。
