Mutagenicity of secondary oxidation products of 8-oxo-7,8-dihydro-2′-deoxyguanosine 5′-triphosphate (8-hydroxy-2′- deoxyguanosine 5′-triphosphate)

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 H2O2, 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 H2O2 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.

► 8-Oxo-7,8-dihydroguanine is oxidized more easily than normal nucleobases. ► MutT is major 8-oxo-7,8-dihydro-dGTPase in Escherichia coli. ► H2O2 treatment of mutT E. coli increased G:C → T:A and A:T → T:A mutations. ► dSpTP and dGhTP were secondary oxidation products of 8-oxo-7,8-dihydro-dGTP. ► Exogenous dSpTP and dGhTP did not significantly increase mutations.