Krewski D, Leroux B G, Bleuer S R, Broekhoven L H
Health Protection Branch, Health & Welfare Canada, Ottawa, Ontario.
Biometrics. 1993 Jun;49(2):499-510.
Of the many short-term tests for mutagenicity that have been proposed in recent years, the Ames Salmonella/microsome assay is the single most widely used and most thoroughly validated in vitro test system. This assay uses cells cultured in a soft agar containing a trace amount of histidine to allow growth of auxotrophic bacteria, and is designed to detect reverse mutations from auxotrophic cells to histidine-independent prototrophic cells. In this paper, statistical models that have been proposed for the analysis of Ames test data are reviewed, including those of a mechanistic and empirical nature. An extension to the class of biologically based models derived by Margolin, Kaplan, and Zeiger (1981, Proceedings of the National Academy of Sciences 78, 3779-3783) is proposed by allowing for diffusion of histidine within the plate agar. Quasi-likelihood methods for estimating the model parameters are presented, and applied to 1,120 data sets from a recent collaborative trial sponsored by the International Programme on Chemical Safety.
在近年来提出的众多短期致突变性测试中，艾姆斯沙门氏菌/微粒体试验是应用最广泛且经过最充分验证的体外测试系统。该试验使用在含有微量组氨酸的软琼脂中培养的细胞，以使营养缺陷型细菌生长，其设计目的是检测从营养缺陷型细胞到不依赖组氨酸的原养型细胞的反向突变。本文回顾了已提出的用于分析艾姆斯试验数据的统计模型，包括那些具有机理性质和经验性质的模型。通过考虑组氨酸在平板琼脂内的扩散，对Margolin、Kaplan和Zeiger（1981年，《美国国家科学院院刊》78, 3779 - 3783）推导的基于生物学的模型类别进行了扩展。提出了用于估计模型参数的拟似然方法，并将其应用于国际化学品安全计划近期发起的一项合作试验的1120个数据集。
