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用于评估致突变性和致癌风险的短期致突变性试验的优点与问题。

Advantages of and problems with short-term mutagenicity tests for the assessment of mutagenic and carcinogenic risk.

作者信息

Ramel C

出版信息

Environ Health Perspect. 1983 Jan;47:153-9. doi: 10.1289/ehp.8347153.

Abstract

The Salmonella microsomal assay has become an indispensible tool for the screening of mutagens and carcinogens, particularly when a large number of samples have to be tested, as in the present context for the screening of air pollution. However, for a more definite identification of potential carcinogens, a verification of the results from bacterial tests has to be performed with a battery of other tests, including point mutations and chromosomal aberrations in eukoaryotic systems. While there is a close qualitative correlation between the mutagenic and carcinogenic property of chemicals, a corresponding quantitative correlation between the mutagenic and carcinogenic potency is not always found. One reason for this lack of quantitative correlation presumably depends on the fact that cancer is induced in two steps, of which only the initiating, but not the promoting, step constitutes a mutational event, which is reflected by mutagenicity tests. Present mutagenicity tests have concentrated on discrete major mutations, while mutations of polygenes, acting on quantitative characters, have largely been omitted. Mutational data from Drosophila indicate, however, that polygenes mutate at a considerably higher rate than major genes and that they have a comparatively strong effect in heterozygous condition. It seems of great importance to develop appropriate methods to study induced mutations of polygenic systems and to get a better understanding of the properties of these genetic systems and an evaluation of the risk connected with induced mutations in polygenes.

摘要

沙门氏菌微粒体试验已成为筛选诱变剂和致癌物不可或缺的工具,尤其是在必须检测大量样品的情况下,就像目前筛选空气污染时的情形。然而,为了更确切地鉴定潜在致癌物,必须用一系列其他试验来验证细菌试验的结果,这些试验包括真核系统中的点突变和染色体畸变。虽然化学品的诱变性和致癌性之间存在密切的定性相关性,但诱变性和致癌效力之间相应的定量相关性并非总是存在。这种缺乏定量相关性的一个原因大概是基于癌症是分两步诱发的这一事实,其中只有起始步骤(而非促进步骤)构成一个突变事件,而这一点在诱变性试验中有所体现。目前的诱变性试验主要集中在离散的主要突变上,而作用于数量性状的多基因的突变在很大程度上被忽略了。然而,来自果蝇的突变数据表明,多基因的突变率比主要基因高得多,而且它们在杂合状态下具有相对较强的效应。开发适当的方法来研究多基因系统的诱导突变,并更好地了解这些遗传系统的特性以及评估与多基因诱导突变相关的风险,似乎非常重要。

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