Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Mutat Res. 2011 Sep 1;714(1-2):11-6. doi: 10.1016/j.mrfmmm.2011.05.015. Epub 2011 Jun 15.
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.
8-氧代-7,8-二氢鸟嘌呤（8-羟基鸟嘌呤）比正常核碱基更容易氧化，这可能产生螺环亚氨基二氢嘧啶（Sp）和胍基二氢嘧啶（Gh）。当这些 8-氧代-7,8-二氢鸟嘌呤的次级氧化产物在 DNA 内形成时，具有高度的诱变作用。为了评估核苷酸池中的 8-氧代-7,8-二脱氧鸟苷 5'-三磷酸（8-羟基-2'-脱氧鸟苷 5'-三磷酸）相应氧化产物的诱变作用，用 H2O2 处理缺乏 mutT 基因的大肠杆菌细胞，并分析诱导的突变。此外，还将 Sp 和 Gh 的 2'-脱氧核苷 5'-三磷酸衍生物引入感受态大肠杆菌细胞。H2O2 处理 mutT 大肠杆菌细胞导致 G:C→T:A 和 A:T→T:A 突变增加。然而，外源性 Sp 和 Gh 2'-脱氧核苷酸的掺入并没有显著增加突变频率。这些结果表明，8-氧代-7,8-二脱氧鸟苷 5'-三磷酸的氧化产物诱导 G:C→T:A 和 A:T→T:A 突变，并且 Sp 和 Gh 的 2'-脱氧核苷 5'-三磷酸衍生物与 DNA 中的碱基相比表现出相当弱的诱变作用。
