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Mutagenicity of secondary oxidation products of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-hydroxy-2'-deoxyguanosine 5'-triphosphate)
| Title: | Mutagenicity of secondary oxidation products of 8-oxo-7,8-dihydro-2'-deoxyguanosine 5'-triphosphate (8-hydroxy-2'-deoxyguanosine 5'-triphosphate) |
| Authors: | Hori, Mika Browse this author | | Suzuki, Tetsuya Browse this author | | Minakawa, Noriaki Browse this author | | Matsuda, Akira Browse this author | | Harashima, Hideyoshi Browse this author | | Kamiya, Hiroyuki Browse this author →KAKEN DB |
| Keywords: | Oxidized nucleotide | | 8-Oxo-7,8-dihydroguanine | | 8-Hydroxyguanine | | Secondary oxidation product | | Spiroiminodihydantoin | | Guanidinohydantoin |
| Issue Date: | 1-Sep-2011 |
| Publisher: | Elsevier B.V. |
| Journal Title: | Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis |
| Volume: | 714 |
| Issue: | 1-2 |
| Start Page: | 11 |
| End Page: | 16 |
| Publisher DOI: | 10.1016/j.mrfmmm.2011.05.015 |
| PMID: | 21704046 |
| 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 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 increases 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. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/48349 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 紙谷 浩之
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