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大肠杆菌中的SOS诱导与沙门氏菌致突变性:330种化合物的比较

SOS induction in Escherichia coli and Salmonella mutagenicity: a comparison using 330 compounds.

作者信息

Mersch-Sundermann V, Schneider U, Klopman G, Rosenkranz H S

机构信息

Department of Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, University of Heidelberg, FRG.

出版信息

Mutagenesis. 1994 May;9(3):205-24. doi: 10.1093/mutage/9.3.205.

Abstract

To examine the concordance of two microbial genotoxicity short-term assays, 330 experimental results for the SOS chromotest using tester strain Escherichia coli PQ37 were compared with the results of the Salmonella/mammalian microsome mutagenicity assay with Salmonella typhimurium TA97, TA98, TA100, TA102, TA104, TA1535, TA1537 and/or TA1538. With respect to qualitative features, the concordance between SOS chromotest and Salmonella mutagenicity test results was 86.4% (sensitivity, 78.6%; specificity, 100%; chi 2 = 188.6). None of the non-mutagens (N = 120) were able to induce the SOS system. Additionally, 45 of the 210 S.typhimurium mutagens (21.5%) did not induce the SOS repair system. On closer examination, the majority of these 45 compounds (84%) were mutagens with activities between 0.001 and 10 rev/nmol. Even though the experimental protocols of both systems were not standardized, the correlation coefficient for the experimental results of the two test systems was 0.7 for the 330 chemicals. Except for aliphatic epoxides (r = 0.47), the mutagenicity/SOS induction correlations for congeneric data sets (polycyclic aromatic hydrocarbons, nitroarenes, nitroarenofurans, mycotins) were even better (r = 0.72-0.95). Additionally, computer automated structure evaluation (CASE) analyses of the nature of the structural determinants associated with each endpoint indicate extensive homologies. The data can be taken to indicate that the two phenomena reflect common mechanisms of action.

摘要

为检验两种微生物遗传毒性短期试验的一致性,将使用测试菌株大肠杆菌PQ37的SOS显色试验的330个实验结果与鼠伤寒沙门氏菌TA97、TA98、TA100、TA102、TA104、TA1535、TA1537和/或TA1538的沙门氏菌/哺乳动物微粒体诱变性试验结果进行了比较。就定性特征而言,SOS显色试验与沙门氏菌诱变性试验结果之间的一致性为86.4%(敏感性为78.6%;特异性为100%;卡方=188.6)。所有非诱变剂(N = 120)均不能诱导SOS系统。此外,210种鼠伤寒沙门氏菌诱变剂中有45种(21.5%)未诱导SOS修复系统。进一步检查发现,这45种化合物中的大多数(84%)是活性在0.001至10 rev/nmol之间的诱变剂。尽管两个系统的实验方案都未标准化,但330种化学物质的两个测试系统实验结果的相关系数为0.7。除脂肪族环氧化物(r = 0.47)外,同类数据集(多环芳烃、硝基芳烃、硝基芳基呋喃、霉菌毒素)的诱变性/SOS诱导相关性甚至更好(r = 0.72 - 0.95)。此外,对与每个终点相关的结构决定因素的性质进行的计算机自动结构评估(CASE)分析表明存在广泛的同源性。这些数据可以表明这两种现象反映了共同的作用机制。

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