Study of Oxidative damages on guanine adducts and hunting of markers for damages on DNA by means of electrochemical methods

电化学方法研究鸟嘌呤加合物氧化损伤及寻找DNA损伤标记物

基本信息

  • 批准号:
    17590035
  • 负责人:
  • 金额:
    $ 1.98万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

Some recent statistical studies in medicine suggest that DNA damages by acetaldehyde (AA) is one of initial actions in carcinogenesis occurred by drinking. Cyclic-propanoguanine (CPrG) will be the most expected candidate as a damaged form in DNA by AA. Based on the theory of electron-hopping along DNA chains through π-π stacking in an oxidative damaging process, I have investigated additional oxidations following the formation of CPrG on DNA as a part of a mis-reading mechanism of base sequences in DNA occurred by CPrG formation by AA.Electrolytic oxidation of CPrG in aqueous media generated a unique dimer compound of CPrG as a major product. Detailed NMR studies indicated that the each CPrG parts had very similar but not same structure representing chemical shifts different a little from each other. Additionally, the linkage sites on each CPrG moieties decided to be certain different positions on CPrG. The expected structure of the dimer has been strongly supported by MS/MS data.The identified structure can be formed by coupling between CPrG itself and a carbocation of CPrG that will be generated via elimination of both two electrons and a proton. This proposed reaction route has been supported by a MO calculation. Conformational studies with MOPAC suggest that the dimer can be formed with an intrastrand mannar and an interstrand manner in DNA and, particularly, the former manner can be attributable to the mis-reading of DNA information.Quite recently I have performed electrolysis of treated DNA double strands (Calf thymus). including CPrG and have found the dimer structure in the treated DNA. The dimer may become an valuable biomarker indicating magnitude of risk of carcinogenesis for drinkers.
近年来的医学统计研究表明,乙醛(AA)对DNA的损伤是饮酒致癌的始动作用之一。环丙鸟嘌呤(CPrG)是AA损伤DNA的最有希望的候选者。基于氧化损伤过程中电子沿沿着DNA链通过π-π堆积的理论,我研究了在DNA上形成CPrG后的额外氧化,作为AA形成CPrG所发生的DNA碱基序列误读机制的一部分。CPrG在水介质中的电解氧化产生了独特的二聚体化合物CPrG作为主要产物。详细的NMR研究表明,每个CPrG部分具有非常相似但不相同的结构,表示化学位移彼此略有不同。此外,每个CPrG部分上的连接位点决定在CPrG上的某些不同位置。二聚体的预期结构得到了MS/MS数据的有力支持。所鉴定的结构可以通过CPrG本身与通过消除两个电子和一个质子产生的CPrG的碳正离子之间的偶联形成。该反应路线得到了分子轨道计算的支持。MOPAC构象研究表明,二聚体可以形成一个intrastrand mannar和interstrand的方式在DNA中,特别是,前者的方式可以归因于DNA信息的误读。包括CPrG,并在处理过的DNA中发现了二聚体结构。二聚体可能成为一个有价值的生物标志物,指示饮酒者致癌风险的大小。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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ESAKA Yukihiro其他文献

Preparation of <i>N</i><sup>2</sup>-Ethyl-2′-deoxyguanosine-<i>d</i><sub>4</sub> as an Internal Standard for the Electrospray Ionization–Tandem Mass Spectrometric Determination of DNA Damage by Acetaldehyde
制备<i>N</i><sup>2</sup>-Ethyl-2-deoxyguanosine-<i>d</i><sub>4</sub>作为电喷雾电离内标– 乙醛造成的 DNA 损伤的串联质谱测定
  • DOI:
    10.2116/analsci.19n034
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    1.6
  • 作者:
    ESAKA Yukihiro;ARUGA Hiromitsu;KUNISHIMA Saki;YAMAMOTO Takuhei;MURAKAMI Hiroya;SAWAMA Yoshinari;SAJIKI Hironao;UNO Bunji
  • 通讯作者:
    UNO Bunji
Development and Evaluation of HILIC-type Sorbents Modified with Hydrophilic Copolymers for Solid-phase Extraction
亲水共聚物改性的固相萃取 HILIC 型吸附剂的开发与评价
  • DOI:
    10.2116/analsci.20p084
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    1.6
  • 作者:
    MURAKAMI Hiroya;SUGIYAMA Takuya;MIKI Yuta;UMEMURA Tomonari;ESAKA Yukihiro;INOUE Yoshinori;TESHIMA Norio
  • 通讯作者:
    TESHIMA Norio
Molding-type Solid-phase Extraction Media Glued with Commercially Available Adhesives
使用市售粘合剂粘合的模压型固相萃取介质
  • DOI:
    10.2116/analsci.20c012
  • 发表时间:
    2020
  • 期刊:
  • 影响因子:
    1.6
  • 作者:
    MIKI Yuta;MURAKAMI Hiroya;IIDA Keisuke;UMEMURA Tomonari;ESAKA Yukihiro;INOUE Yoshinori;TESHIMA Norio
  • 通讯作者:
    TESHIMA Norio
Anionic polymerization of monomers carrying adamantyl groups
带有金刚烷基的单体的阴离子聚合
  • DOI:
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    ESAKA Yukihiro;KUNISHIMA Saki;ARUGA Hiromitsu;YAMAMOTO Takuhei;MURAKAMI Hiroya;TESHIMA Norio;UNO Bunji;Takashi Ishizone
  • 通讯作者:
    Takashi Ishizone
カルボン酸とα-(ハロメチル)アクリル酸エステルの共役置換反応を用いた架橋ポリマーの合成と解架橋
利用羧酸和α-(卤甲基)丙烯酸酯的共轭取代反应合成和解交联交联聚合物
  • DOI:
  • 发表时间:
    2021
  • 期刊:
  • 影响因子:
    0
  • 作者:
    ESAKA Yukihiro;KUNISHIMA Saki;ARUGA Hiromitsu;YAMAMOTO Takuhei;MURAKAMI Hiroya;TESHIMA Norio;UNO Bunji;Takashi Ishizone;北河 大葵,大矢 高史,高坂 泰弘
  • 通讯作者:
    北河 大葵,大矢 高史,高坂 泰弘

ESAKA Yukihiro的其他文献

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{{ truncateString('ESAKA Yukihiro', 18)}}的其他基金

Development of ultra sensitive CE-ESI-MS methods based on the nano-focusng stratedy
基于纳米聚焦策略的超灵敏CE-ESI-MS方法的开发
  • 批准号:
    15K05546
  • 财政年份:
    2015
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Study of Sequentially Carrier-replacing Electrokinetic Chromatography as a Platform for Custom-made Separation Systems
连续载体取代动电色谱作为定制分离系统平台的研究
  • 批准号:
    20550082
  • 财政年份:
    2008
  • 资助金额:
    $ 1.98万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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