James D A, Smith D M
Mutat Res. 1982 Aug;97(4):303-14. doi: 10.1016/0165-1161(82)90029-2.
A dominant lethal (DL) mutation is a genetic change that results in the death of the conceptus that inherits it. The assay is normally carried out in mice and the production of DL mutation by the test chemical is characterised by an increase in non-viable embryos. A distinct advantage of the DL assay is that it is an in vivo, mammalian, germ cell assay and is therefore pertinent to the fundamental question of chemical mutagenesis, i.e.: is a chemical likely to produce genetic changes that can be transferred to the offspring? The two principal criticisms of the assay are that the main type of genetic damage it detects is chromosomal breakage that leads to death of the conceptus, and that the assay is considered to be relatively insensitive. The Association of the British Pharmaceutical Industry (ABPI) Working Party on Mutagenicity was established in 1974. Its principal objective was to consider the problem of mutagenicity and associated matters in relation to the development of new medicines and to make recommendations and proposals for collaborative work if indicated. The dominant lethal assay is one of several tests for mutagenicity chosen for evaluation by collaborative study. The objective of the collaborative study was to gain more information about the validity and dependability of the dominant lethal assay. The present report concerns an analysis of the differences between compounds, laboratories and statistical methods utilising the data from the collaborative study.
显性致死（DL）突变是一种导致继承该突变的受精卵死亡的基因变化。该试验通常在小鼠中进行，受试化学物质产生的DL突变的特征是不可存活胚胎数量增加。DL试验的一个明显优势在于它是一种体内哺乳动物生殖细胞试验，因此与化学诱变的基本问题相关，即：一种化学物质是否可能产生可传递给后代的基因变化？对该试验的两个主要批评是，它检测到的主要遗传损伤类型是导致受精卵死亡的染色体断裂，并且该试验被认为相对不敏感。英国制药工业协会（ABPI）致突变性工作组于1974年成立。其主要目标是考虑与新药开发相关的致突变性问题及相关事宜，并在必要时就合作研究提出建议和提议。显性致死试验是被选用于合作研究评估的几种致突变性试验之一。合作研究的目的是获取更多关于显性致死试验有效性和可靠性的信息。本报告涉及利用合作研究数据对化合物、实验室和统计方法之间差异的分析。
