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首页> 外文期刊>Mutation Research, A. Reviews in Genetic Toxicology >The performance of short-term tests in identifying potential germ cell mutagens: a qualitative and quantitative analysis
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The performance of short-term tests in identifying potential germ cell mutagens: a qualitative and quantitative analysis

机译：短期测试在识别潜在生殖细胞诱变剂中的性能：定性和定量分析

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A retrospective analysis was undertaken to assess the performance of selected short-term tests in the discrimination of mammalian germ cell mutagens and nonmutagens using data derived from the U.S. Environmental Protection Agency/International Agencyfor Research on Cancer Genetic Activity Profile (EPA/IARC GAP) and EPA GENE-TOX databases. The short-term tests selected were gene mutation in Salmonella (S. typhimurium), cultured mammalian cell gene mutation and chromosomal aberrations, and mammalian bone marrow cytogene.tics (micronucleus and chromosomal aberrations). These are the first level tests Used in the EPA mutagenicity testing guidelines. The results of this analysis showed good sensitivity of short-term in vitro tests for mammalian cell gene mutation (96%) or chromosomal aberrations (92%) in identifying germ cell mutagens, while the sensitivity of tests for gene mutation in S. typhimurium was lower (79%). Bone marrow micronucleus or chromosomal aberration assays in vivo each displayed a sensitivity of 96%. Thus, both the in vitro and in vivo tests may be used effectively to screen chemicals for potential germ cell mutagenicity, In contrast, the in vitro tests mentioned above performed .poorly in discriminating putative germ cell nonmutagens, giving results for specificity at or below what is expected due to chance alone (50-11 %). The bone marrow assays were more efficient in this regard, the micronucleus test yielding a specificity of 63% and the chromosomal aberrations assay 64%. The mouse bone marrow micronucleus test also performed well on a quantitative basis, responding at or below the lowest effective doses tested in the mouse dominant lethal assay. Regression analysis of the mean lowest effective doses of chemicals evaluated invivo showed approximately 1:1 linear correlations for mouse germ cell assays (heritable translocation vs dominant lethal or specific locus tests) as well as for mouse bone marrow assays (micronucleus vs chromosomal aberration). The results suggest the value of the bone marrow micronucleus test as an assay for potential germ cell mutagenicity and the dominant lethal test as a relatively inexpensive choice for confirmation of germ cell damage. The sensitivity of the in vitro assays investigated and the discriminatory capability of the in vivo bone marrow assay affirmed the utility of these tests'within the framework of the EPA mutagenicity testing guidelines.
机译：进行回顾性分析，使用美国环境保护署/国际癌症遗传活性谱研究机构（EPA / IARC GAP）和EPA GENE-TOX数据库。选择的短期测试是沙门氏菌（鼠伤寒沙门氏菌）中的基因突变，培养的哺乳动物细胞基因突变和染色体畸变，以及哺乳动物骨髓细胞遗传学（微核和染色体畸变）。这些是EPA致突变性测试指南中使用的第一级测试。该分析的结果表明，对哺乳动物细胞基因突变（96％）或染色体畸变（92％）的短期体外测试在鉴定生殖细胞诱变剂方面具有很高的敏感性，而鼠伤寒沙门氏菌基因突变的测试灵敏度较高。较低（79％）。体内的骨髓微核或染色体畸变分析各自显示出96％的灵敏度。因此，体外和体内试验都可以有效地用于筛选化学物质以检测潜在的生殖细胞致突变性。相反，上述体外试验在鉴别推定的生殖细胞非突变体方面效果较差，给出的特异性结果为或低于预计仅由于偶然性（50-11％）。在这方面，骨髓检测更有效，微核检测产生的特异性为63％，染色体畸变检测为64％。小鼠骨髓微核试验在定量基础上也表现良好，在或低于小鼠显性致死试验中测试的最低有效剂量时反应良好。在体内评估的化学药品的平均最低有效剂量的回归分析显示，小鼠生殖细胞测定（遗传易位与显性致死或特定基因座测定）以及小鼠骨髓测定（微核与染色体畸变）之间的线性关系约为1：1。结果表明，骨髓微核试验可作为潜在生殖细胞致突变性的一种测定方法，显性致死试验可作为确认生殖细胞损伤的相对便宜的选择。在EPA致突变性测试指南的框架内，所研究的体外试验的敏感性以及体内骨髓试验的区分能力证实了这些试验的实用性。

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