A comparison of mutation spectra detected by the Escherichia coli lac(+) reversion assay and the Salmonella typhimurium his(+) reversion assay.
Each of the Escherichia coli tester strains in the WP3101P-WP3106P series contains an F' plasmid with a different base substitution mutation within the lacZ gene. Each of the six possible base substitution mutations, therefore, can be assayed with these strains by Lac(+) reversion. We used the strains to characterize the mutational profiles of 21 chemical mutagens, including alkylating agents, base analogs and oxidative compounds. We also assayed the mutagens with Salmonella typhimurium tester strains TA7002, TA7004 and TA7005, which detect A.T-->T.A, G.C-->A.T and G.C-->T.A mutations, respectively, and we compared the sensitivity and specificity of the two systems. Escherichia coli strain WP3102P was more sensitive than the S.TYPHIMURIUM: strains to G.C-->A.T transitions induced by N(4)-aminocytidine, 5-azacytidine, cumene hydroperoxide (CHP), t-butyl hydroperoxide (BHP), N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG), methyl methane sulfonate and N-ethyl-N-nitrosourea (ENU), while the reverse was true for G.C-->A.T transitions induced by 2-aminopurine and phosmet. Escherichia coli strain WP3104P, which detects G.C-->T.A transversions, was superior to the S.TYPHIMURIUM: strains in detecting transversions induced by N(4)-aminocytidine, 5-azacytidine, 5-diazouracil, CHP, BHP, ENNG, ENU, 4-nitroquinoline 1-oxide (4-NQO) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Escherichia coli WP3105P was also more sensitive than S. TYPHIMURIUM: to A.T-->T.A transversions induced by N-methyl-N- nitrosourea (MNU), CHP and 4-NQO, but it was less sensitive to those induced by ENNG, ENU and 2-aminopurine. The present results indicate that the E.COLI: Lac(+) reversion system with tester strains WP3101P-WP3106P is as sensitive as the S.TYPHIMURIUM: His(+) reversion system for the detection of specific mutations induced by a variety of direct mutagens.
Ohta
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T
School of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan. onta@ls.toyaku.ac.jp
Watanabe-Akanuma
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Yamagata
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H
D015075:2-Aminopurine / Q000378:metabolism; D015112:4-Nitroquinoline-1-oxide / Q000378:metabolism; D000477:Alkylating Agents / Q000378:metabolism; D001374:Azacitidine / Q000378:metabolism; D001555:Benzene Derivatives / Q000378:metabolism; D003562:Cytidine / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000187:drug effects; D004252:DNA Mutational Analysis / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000235:genetics*; D005038:Ethylnitrosourea / Q000378:metabolism; D005557:Formaldehyde / Q000378:metabolism; D005663:Furans / Q000378:metabolism; D005668:Furylfuramide / Q000378:metabolism; D006037:Glyoxal / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D007763:Lac Operon / Q000235:genetics; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives / Q000378:metabolism; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D016877:Oxidants / Q000378:metabolism; D010706:Phosmet / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation / Q000187:drug effects; D012486:Salmonella typhimurium / Q000235:genetics*; D019810:Sodium Azide / Q000378:metabolism; D014498:Uracil / Q000031:analogs & derivatives / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000378:metabolism
D000477:Alkylating Agents; D001555:Benzene Derivatives; D005663:Furans; D009153:Mutagens; D016877:Oxidants; D005668:Furylfuramide; D008769:Methylnitronitrosoguanidine; C004758:5-diazouracil; D005557:Formaldehyde; C013525:ENNG; D015075:2-Aminopurine; D006639:Histidine; D006037:Glyoxal; D015112:4-Nitroquinoline-1-oxide; D014498:Uracil; C038769:N(4)-aminocytidine; D003562:Cytidine; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; D004247:DNA; D020122:tert-Butylhydroperoxide; D019810:Sodium Azide; D001374:Azacitidine; D005038:Ethylnitrosourea; C007164:cumene hydroperoxide; D010706:Phosmet