Abstract
Purpose: 8-Hydroxyguanine (8-oxo-7,8-dihydroguanine) is oxidized more easily than the normal nucleobases and further oxidation products are generated. Spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) are secondary oxidation products of 8-hydroxyguanine and highly mutagenic when they are formed in DNA. In this study, we evaluated mutagenicity of oxidation products of 8-hydroxy-2'-deoxyguanosine 5'-triphosphate (8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate) in Escherichia coli cells.
Methods: E. coli cells deficient in the mutT gene were treated with H2O2 and induced mutations were analyzed. Moreover, the 2'-deoxyriboside 5'-triphosphate derivatives of Sp and Gh were introduced into competent E. coli.
Results: The H2O2 treatment of mutT E. coli cells resulted in increase of G:C-->C:G and G:C-->A:T mutations instead of decreased A:T-->C:G mutations. However, none of the Sp and Gh 2'-deoxyribonucleotides significantly increased mutation frequency.
Conclusions: These results suggested that oxidation product(s) of 8-hydroxy-2'-deoxyguanosine 5'-triphosphate induces G:C-->C:G and G:C-->A:T mutations and that the 2'-deoxyriboside 5'-triphosphate derivatives of Sp and Gh are weakly mutagenic in contrast to the bases in DNA.
