PMID- 11934440 OWN - NLM STAT- MEDLINE DCOM- 20020624 LR - 20190702 IS - 0027-5107 (Print) IS - 0027-5107 (Linking) VI - 501 IP - 1-2 DP - 2002 Apr 25 TI - Salmonella typhimurium mutagenicity tester strains that overexpress oxygen-insensitive nitroreductases nfsA and nfsB. PG - 79-98 AB - We have designed and constructed a series of plasmids that contain the major and/or minor Escherichia coli nitroreductase genes, nfsA and nfsB, in different combinations with R plasmid mucA/B genes and the Salmonella typhimurium OAT gene. The plasmid encoded gene products are necessary for both the metabolic activation of a range of structurally diverse nitrosubstituted compounds, and for mutagenic translation bypass. Introduction of these plasmids into S. typhimurium TA1538 and TA1535 has created several new tester strains which exhibit an extremely high mutagenic sensitivity and a broad substrate specificity towards a battery of nitrosubstituted test compounds that included 4-nitroquinoline-1-oxide (4-NQO), nitrofurazone (NF), 1-nitropyrene (1-NP), 2-nitronaphthalene (2-NN), 2-nitrofluorene (2-NF), and 1,6-dinitropyrene (1,6-DNP). Our studies show that the nfsA gene encodes a product that is extremely effective in the metabolic activation of a range of structurally diverse nitrosubstituted compounds. Several of the new tester strains are more than two orders of magnitude more sensitive to nitrosubstituted compounds than the Ames tester strains TA100 or TA98. In addition to enhancing mutagenic sensitivity, plasmids encoding both metabolic and mutagenesis functions on a single plasmid provide considerable flexibility for future mechanistic studies or tester strain development, in which it may be necessary to introduce additional plasmids containing different antibiotic resistance markers. FAU - Carroll, C C AU - Carroll CC AD - Biology Department, Carleton University, 1125 Colonel By Drive, Ont., Ottawa, Canada. FAU - Warnakulasuriyarachchi, D AU - Warnakulasuriyarachchi D FAU - Nokhbeh, M R AU - Nokhbeh MR FAU - Lambert, I B AU - Lambert IB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - Mutat Res JT - Mutation research JID - 0400763 RN - 0 (Bacterial Proteins) RN - 0 (Escherichia coli Proteins) RN - 0 (MucA protein, Bacteria) RN - 0 (MucB protein, Bacteria) RN - 0 (Nitro Compounds) RN - EC 1.7.- (NfsA protein, E coli) RN - EC 1.7.- (NfsB protein, E coli) RN - EC 1.7.- (Nitroreductases) SB - IM MH - Bacterial Proteins/genetics MH - *Drug Resistance, Neoplasm MH - Escherichia coli MH - *Escherichia coli Proteins MH - *Mutagenicity Tests MH - Nitro Compounds/toxicity MH - Nitroreductases/biosynthesis/*genetics MH - Plasmids MH - Salmonella typhimurium/*genetics MH - Sensitivity and Specificity EDAT- 2002/04/06 10:00 MHDA- 2002/06/25 10:01 CRDT- 2002/04/06 10:00 PHST- 2002/04/06 10:00 [pubmed] PHST- 2002/06/25 10:01 [medline] PHST- 2002/04/06 10:00 [entrez] AID - S0027510702000180 [pii] AID - 10.1016/s0027-5107(02)00018-0 [doi] PST - ppublish SO - Mutat Res. 2002 Apr 25;501(1-2):79-98. doi: 10.1016/s0027-5107(02)00018-0.