title: Mutagenicity of secondary oxidation products of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-hydroxy-2'- deoxyguanosine 5'-triphosphate).
abstract: 8-Oxo-7,8-dihydroguanine (8-hydroxyguanine) is oxidized more easily than normal nucleobases, which can produce spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). These secondary oxidation products of 8-oxo-7,8-dihydroguanine are highly mutagenic when formed within DNA. To evaluate the mutagenicity of the corresponding oxidation products of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-hydroxy-2'- deoxyguanosine 5'-triphosphate) in the nucleotide pool, Escherichia coli cells deficient in the mutT gene were treated with H(2)O(2), and the induced mutations were analyzed. Moreover, the 2'-deoxyriboside 5'-triphosphate derivatives of Sp and Gh were also introduced into competent E. coli cells. The H(2)O(2) treatment of mutT E. coli cells resulted in increase of G:C → T:A and A:T → T:A mutations. However, the incorporation of exogenous Sp and Gh 2'-deoxyribonucleotides did not significantly increase the mutation frequency. These results suggested that the oxidation product(s) of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate induces G:C → T:A and A:T → T:A mutations, and that the 2'-deoxyriboside 5'-triphosphate derivatives of Sp and Gh exhibit quite weak mutagenicity, in contrast to the bases in DNA.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Hori
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Noriaki
authors.initials: N
authors.lastname: Minakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Harashima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kamiya
mesh_terms: D003848:Deoxyguanine Nucleotides / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics; D029968:Escherichia coli Proteins / Q000378:metabolism; D006146:Guanidines / Q000633:toxicity; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives / Q000633:toxicity; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006827:Hydantoins / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000633:toxicity
chemical_list: D003848:Deoxyguanine Nucleotides; D029968:Escherichia coli Proteins; D006146:Guanidines; D006827:Hydantoins; D009153:Mutagens; D013141:Spiro Compounds; C467338:guanidinohydantoin; C408822:spiroiminodihydantoin; D006151:Guanosine; C078206:8-oxodeoxyguanosine triphosphate; C057674:8-hydroxyguanosine triphosphate; C024829:8-hydroxyguanine; D006147:Guanine; D006160:Guanosine Triphosphate; D006861:Hydrogen Peroxide