Studies of neighboring base damage induced by oxidation of synthetic DNAs containing oxidatively damaged bases

含有氧化损伤碱基的合成 DNA 氧化诱导邻近碱基损伤的研究

• 批准号: 10671979
• 负责人: INOUE Hideo
• 金额: $ 1.98万
• 依托单位: Osaka City University (1999)Hokkaido University (1998)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671979/
• 关键词: DNAs containing damaged bases; 8-oxoguanine; 8-oxoadenine; KMnOィイD24ィエD2 oxidation; neighboring base damage; reaction mechanism; KMnO_4酸化; DNA損傷; 酸化損傷塩基の酸化; 過マンガン酸カリウム; 5-ヒドロキシウラシル; 5-ヒドロキシシトシン; 損傷塩基近傍の塩基損傷

Recently we found that KMnOィイD24ィエD2 oxidation of DNA oligomers containing a 7,8-digydro-8-oxoguanine (8-oxo-G) residue induces damage to the neighboring base residues. The present data from several experiments suggested that a redox reaction involving the 8-oxo-G initiates damage: the reactivity of the DNA bases at the site 5'-adjacent to the 8-oxo-G was in the order G > A > T, C, and this preference correlates with the electron donating abilities of the bases. The present study also indicated that other oxidatively damaged bases, 7,8-dihydro-8-oxoadenine (8-oxo-A), 5-hydroxyuracil (5-oh-U) and 5-hydroxycytosine (5-oh-C) show similar behavior in DAN. On the other hand, in order to examine the pathways and the intermediates for the oxidative degradation of 8-oxo-G and 8-oxo-A, we have carried out the KMnOィイD24ィエD2 oxidation using 8-oxo-2'-deoxy-guanosine and -adenosine derivatives as a model. The reactions gave three major products, respectively, and we have determined the structures of the products. Based on the structures, we deduced active oxidation intermediates from the 8-oxo-purines (in DNA) which may be involved in the redox reaction as electron acceptors.

最近，我们发现，高锰酸钾氧化含有7，8-二氢-8-氧代鸟嘌呤（8-oxo-G）残基的DNA寡聚体会导致相邻碱基残基的损伤。从几个实验的数据表明，涉及8-氧代-G的氧化还原反应引发损伤：在5 '-邻近8-氧代-G的位点处的DNA碱基的反应性的顺序是G > A > T，C，并且这种偏好与碱基的供电子能力相关。本研究还表明，其他氧化损伤的碱基，7，8-二氢-8-氧代腺嘌呤（8-oxo-A），5-羟基尿嘧啶（5-oh-U）和5-羟基胞嘧啶（5-oh-C）在DAN中表现出类似的行为。另一方面，为了研究8-oxo-G和8-oxo-A氧化降解的途径和中间体，我们使用8-oxo-2 '-deoxy-guanosine和-adenosine衍生物作为模型，进行了KMnO氧化物D24氧化物D2的氧化。这些反应分别得到了三种主要产物，并确定了产物的结构。基于这些结构，我们推测DNA中的8-氧代嘌呤可能作为电子受体参与氧化还原反应。

项目成果

Shiro Koizume, Hideo Inoue, Hiroyuki Kamiya and Eiko Ohtsuka: "Neighboring base damage induced by permanganate oxidation of 8-oxoguanine in DNA"Nucleic Acids Res.. 26・15. 3599-3607 (1998)

Shiro Koizume、Hideo Inoue、Hiroyuki Kamiya 和 Eiko Ohtsuka：“DNA 中 8-氧代鸟嘌呤的高锰酸盐氧化诱导的邻近碱基损伤”《核酸研究》26・15（1998）。

Shiro Koizume: "Neighboring base damage induced by permanganate oxidation of 8-oxoguamine in DNA"Nucleic Acids Research. 26. 3599-3607 (1998)

Shiro Koizume：“DNA 中 8-oxoguamine 的高锰酸盐氧化诱导的邻近碱基损伤”核酸研究。

Masayoshi Fukuoka, Hideo Inoue, Takahiro Yamauchi, Shiro Koizume and Eiko Ohtsuka: "Isolation and characterization of the products from KMnOィイD24ィエD2 oxidation of an 8-oxo-2'-deoxyguanosine derivative"Nucleic Acids Symp.Ser.. No.39. 233-234 (1998)

Masayoshi Fukuoka、Hideo Inoue、Takahiro Yamauchi、Shiro Koizume 和 Eiko Ohtsuka：“8-oxo-2-脱氧鸟苷衍生物的 KMnO-D24-D2 氧化产物的分离和表征”Nucleic Acids Symp.Ser. No. 39. 233-234 (1998)

Shiro Koizume: "Neighboring base damage induced by permanganate oxidation of 8-oxoguanine in DNA"Nucleic Acids Research. 26・5. 3599-3607 (1998)

小泉史郎：“DNA 中 8-氧代鸟嘌呤的高锰酸盐氧化诱导的邻近碱基损伤”《核酸研究》26・5（1998）。

Masayoshi Fukuoka: "Isolation and characterization of the products from KMnO4 osidation of an 8-oxo-2-deoxyguanosine derivative"Nucleic Acids Symposium series. 39(号). 233-234 (1998)

Masayoshi Fukuoka：“8-氧代-2-脱氧鸟苷衍生物的 KMnO4 氧化产物的分离和表征”核酸研讨会系列 39（期）（1998 年）。