SOS induction in Escherichia coli and Salmonella mutagenicity: a comparison using 330 compounds.
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.
Mersch-Sundermann
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Department of Microbiology and Hygiene, Faculty of Clinical Medicine Mannheim, University of Heidelberg, FRG.
Schneider
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Klopman
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Rosenkranz
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D000818:Animals; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics*; D005069:Evaluation Studies as Topic; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods* / Q000706:statistics & numerical data; D009153:Mutagens / Q000633:toxicity; D051381:Rats; D013014:SOS Response, Genetics / Q000187:drug effects* / Q000235:genetics; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000235:genetics*; D012680:Sensitivity and Specificity
D009153:Mutagens