Ray V A, Kier L D, Kannan K L, Haas R T, Auletta A E, Wassom J S, Nesnow S, Waters M D
Mutat Res. 1987 May;185(3):197-241. doi: 10.1016/0165-1110(87)90018-2.
This report of the Gene-Tox Assessment Panel is a compilation of data that documents the chemical testing efforts in genetic toxicology through mid-1979. It thus provides an historical perspective of the major efforts in this field and the utility of test models. The total number of chemicals tested in assays reflects chemical availability, commercial interest in specific structural types, the ease or difficulty in assay performance, as well as methodological development resulting from testing experience. Other factors that have been important in assay selection and utility are the perceptions of relevance to hazard evaluation of chemicals and the role that genetic factors may have in other disease states as well as in heritable defects. The phylogenetic diversity of test systems attests to the tremendous effort that has been applied to the testing and evaluation of the effect chemicals can have on genetic structure. The data also illustrate the fact that certain chemicals have an intrinsic capability to alter the genetic structure of cells of diverse biological origin in an heritable manner, whereas others do not. Any attempt to summarize and analyze a data base of this magnitude is a formidable task that would be almost impossible without a computer capability. A computerized system of analysis has been developed at the Environmental Mutagen Information Center (EMIC) that makes it possible to examine the performance of any particular assay in any of 30 chemical classes and to make comparisons with all the other assays individually or in designated groupings. Components of this system include: A distribution of the 2622 chemicals into 30 chemical classes with results of testing in each class. A tabulation of assay results showing the total numbers of chemicals tested, with their definitive and nondefinitive results. A subdivision of assays and results of testing into four major groups: gene mutation, chromosomal aberrations, other genotoxic effects, and in vitro cell transformation assays. These major groups are further subdivided into phylogenetic categories and type of assay. A system of analysis of results utilizing mutagenicity and carcinogenicity comparisons and phylogenetic concordance and discordance. The major utility and/or benefit of this compilation will be derived from a chemical class by chemical class comparative analysis of individual assay performance. Obviously, the data base will serve as a resource for safety evaluation of chemicals through structural correlations and biological end point analyses.(ABSTRACT TRUNCATED AT 400 WORDS)
基因毒性评估小组的这份报告汇编了截至1979年年中记录遗传毒理学化学测试工作的数据。因此,它提供了该领域主要工作以及测试模型实用性的历史视角。检测中所测试化学品的总数反映了化学品的可得性、对特定结构类型的商业兴趣、检测操作的难易程度,以及测试经验带来的方法学发展。在检测选择和实用性方面起重要作用的其他因素包括对化学品危害评估相关性的认知,以及遗传因素在其他疾病状态和遗传缺陷中可能发挥的作用。测试系统的系统发育多样性证明了在测试和评估化学品对遗传结构可能产生的影响方面付出的巨大努力。数据还说明了这样一个事实,即某些化学品具有以可遗传方式改变不同生物来源细胞遗传结构的内在能力,而其他化学品则没有。任何试图总结和分析如此大量数据库的尝试都是一项艰巨的任务,没有计算机能力几乎是不可能完成的。环境诱变信息中心(EMIC)开发了一个计算机化分析系统,使得能够检查30个化学类别中任何一类中任何特定检测的性能,并与所有其他检测进行单独或指定分组的比较。该系统的组成部分包括:将2622种化学品分布到30个化学类别中,并列出每个类别的测试结果。列出检测结果的表格,显示所测试化学品的总数及其明确和不明确的结果。将检测和测试结果细分为四个主要组:基因突变、染色体畸变、其他遗传毒性效应和体外细胞转化检测。这些主要组进一步细分为系统发育类别和检测类型。利用致突变性和致癌性比较以及系统发育一致性和不一致性的结果分析系统。这份汇编的主要实用性和/或益处将来自对各个检测性能进行逐个化学类别比较分析。显然,该数据库将通过结构相关性和生物学终点分析作为化学品安全评估的资源。(摘要截取自400字)