The mutations induced by oxidatively damaged nucleotides, 5-formyl-dUTP and 5-hydroxy-dCTP,in Escherichia coli.
The mutational properties of 5-formyl-2'-deoxyuridine 5'-triphosphate (5-CHO-dUTP) and 5-hydroxy-2'-deoxycytidine 5'-triphosphate (5-OH-dCTP), the major oxidatively damaged pyrimidine nucleotides derived from dTTP and dCTP, respectively, were analyzed by an in vivo assay. 5-CHO-dUTP and 5-OH-dCTP were directly incorporated into Escherichia coli , and their mutagenicities were evaluated by the chromosomal lacI forward mutation assay. The mutation frequencies increased, depending on the dose of these damaged nucleotides, indicating that these nucleotides were incorporated into E.coli and acted as mutagens in vivo . The mutagenicities of 5-CHO-dUTP and 5-OH-dCTP were comparable to that of 8-hydroxy-2'-deoxyguanosine 5'-triphosphate, a major form of dGTP oxidative damage. 5-CHO-dUTP induced G.C to A.T, A.T to G.C and G.C to T.A mutations, and 5-OH-dCTP elicited G.C to A.T, A.T to C.G and G.C to T.A mutations.
Fujikawa
K
K
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Kamiya
H
H
Kasai
H
H
D001426:Bacterial Proteins / Q000235:genetics; D004252:DNA Mutational Analysis; D004260:DNA Repair; D003838:Deoxyadenine Nucleotides / Q000378:metabolism; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D003845:Deoxycytosine Nucleotides / Q000378:metabolism* / Q000494:pharmacology; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D003856:Deoxyuracil Nucleotides / Q000378:metabolism* / Q000494:pharmacology; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics*; D029968:Escherichia coli Proteins; D016680:Genome, Bacterial; D056968:Lac Repressors; D008957:Models, Genetic; D016296:Mutagenesis / Q000187:drug effects; D009693:Nucleic Acid Hybridization; D016877:Oxidants / Q000494:pharmacology; D017354:Point Mutation; D012097:Repressor Proteins / Q000235:genetics; D017422:Sequence Analysis, DNA; D013942:Thymine Nucleotides / Q000378:metabolism
D001426:Bacterial Proteins; D003838:Deoxyadenine Nucleotides; D003845:Deoxycytosine Nucleotides; D003848:Deoxyguanine Nucleotides; D003856:Deoxyuracil Nucleotides; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D016877:Oxidants; D012097:Repressor Proteins; D013942:Thymine Nucleotides; D003841:Deoxycytidine; C027078:deoxyuridine triphosphate; C024107:2'-deoxycytidine 5'-triphosphate; C061519:5-formyl-2'-deoxyuridine; C074071:5-hydroxy-2'-deoxycytidine; C029603:deoxyguanosine triphosphate; C026600:2'-deoxyadenosine triphosphate; C024157:thymidine 5'-triphosphate; D003857:Deoxyuridine