Effects of DNA repair deficiency on the mutational specificity in the lacZ gene of Escherichia coli.
The mutational specificities of various chemical mutagens were compared in isogenic E. coli strains with different DNA repair capabilities (wild-type, uvrA, umuC, and uvrA umuC) in a reversion assay employing a set of mutant lacZ genes that can detect two types of transitions, four types of transversions, and five kinds of specific frameshift events. A uvrA derivative was more sensitive than the wild-type strain to 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone for +1G, -1G, -2(C-G), +1A and -1A frameshifts, G.C-->A.T transitions, and G.C-->T.A transversions. In a uvrA background, G.C-->T.A transversions and +1G, +1A, and -1A frameshifts appeared to be umuC-dependent, while G.C-->A.T transitions were not. N-Ethyl-N'-nitro-N-nitrosoguanidine was more mutagenic in a uvrA background for five kinds of frameshifts and G.C-->A.T transitions, but not for G.C-->T.A, A.T-->C.G, and A.T-->G.C base substitutions. A.T-->C.G transversions were totally dependent on umuC gene function. For the investigation of mutational specificities induced by frameshift mutagens, an rfa mutation was additionally introduced. The rfa strain responded to 2-nitrofluorene, which induced primarily -2(C-G) frameshift mutations. In an rfa uvrA background, benzo[a]pyrene induced +1G, -1G, +1A, and -1A frameshifts. 2-Aminoanthracene induced +1G, -1G, and +1A, but not -1A, frameshifts, with -1G frameshifts predominating. Ethidium bromide induced only two types of frameshifts, -1G and +1A. Frameshifts induced by ICR-170 were independent of umuC gene function, while those by induced 1-nitropyrene were partly umuC-dependent.
Watanabe-Akanuma
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Laboratory of Genetic Toxicology, Institute of Environmental Toxicology, Tokyo, Japan.
Ohta
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T
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000609:Aminoacridines; D000873:Anthracenes / Q000633:toxicity; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000633:toxicity; D011088:DNA Ligases / Q000172:deficiency; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase; D004926:Escherichia coli / Q000187:drug effects; D029968:Escherichia coli Proteins; D004996:Ethidium; D005449:Fluorenes / Q000633:toxicity; D016368:Frameshift Mutation; D005663:Furans / Q000633:toxicity; D005798:Genes, Bacterial; D016695:Glycosyltransferases; D007763:Lac Operon / Q000187:drug effects*; D008727:Methotrexate / Q000633:toxicity; D008769:Methylnitronitrosoguanidine / Q000031:analogs & derivatives / Q000633:toxicity; D016296:Mutagenesis; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity; D009588:Nitrogen Mustard Compounds / Q000633:toxicity; D017354:Point Mutation; D011721:Pyrenes; D013045:Species Specificity; D013489:Suppression, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D000609:Aminoacridines; D000873:Anthracenes; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D005449:Fluorenes; D005663:Furans; D009153:Mutagens; D009588:Nitrogen Mustard Compounds; D011721:Pyrenes; C091910:acridine mustard; D008769:Methylnitronitrosoguanidine; C019499:2-nitrofluorene; D001564:Benzo(a)pyrene; C013525:ENNG; C054121:3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone; C006593:2-anthramine; C078202:UmuC protein, E coli; D016695:Glycosyltransferases; C080934:lipooligosaccharide 1,5-heptosyltransferase; D004259:DNA-Directed DNA Polymerase; C055218:UmuD protein, E coli; D001616:beta-Galactosidase; C068631:UvrA protein, E coli; D000251:Adenosine Triphosphatases; D011088:DNA Ligases; D004996:Ethidium; C032668:1-nitropyrene; D008727:Methotrexate