MECHANISTIC STUDIES OF OXYGEN PATHOLOGY

氧病理学的机制研究

• 批准号: 2734601
• 负责人: THOMAS A DIX
• 金额: $ 15.04万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-04-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2734601
• 关键词: DNA damage; chemical reaction; gas chromatography mass spectrometry; high performance liquid chromatography; hydroxyl radical; metals; nitric oxide; nucleic acid sequence; nucleosides; oligonucleotides; oxidation; oxidizing agents; peroxides; plasmids; superoxides

DESCRIPTION: These studies will employ specific methods for generation of hydroxyl radicals, hydroperoxyl radicals (and superoxide), and peroxyl radicals to examine the reactions of these three species with DNA. The first specific aim will examine the reactions of specific oxidants with oxynucleosides, homooligodeoxynucleotides, and homooligodeoxynucleotide complexes. Products will be analyzed by GC-MS and HPLC with electrochemical detection. The second specific aim will examine the mechanisms by which the oxidants cleave the DNA backbone by oxidizing the deoxyribose moiety. Specific products indicative of the site of radical attack will be identified. This aim also will investigate the sequence specificity of DNA oxidation by oxidants in specific fragments of a Bluescript plasmid. The third specific aim will investigate the effects of metals, organic hydroperoxides, and nitric oxide on the nature and distribution of products formed in deoxynucleosides, oligodeoxynucleotides, and DNA fragments. The proposed studies will identify marker products for oxidant-specific DNA damage and provide broader insights into the roles of oxidants in disease.

描述：这些研究将使用特定的方法来生成 羟基自由基、氢过氧自由基(和超氧化物)和过氧基 自由基来检测这三个物种与DNA的反应。这个 第一个特定目标将检查特定氧化剂与 氧合核苷、同源脱氧核苷酸和同源脱氧核苷酸 复合体。产物用气相色谱-质谱仪和电化学法测定。 侦测。第二个具体目标将审查通过哪些机制 氧化剂通过氧化脱氧核糖部分来切割DNA主干。 指示激进攻击地点的特定产品将是 确认身份。这一目标还将研究DNA的序列特异性 蓝质粒特定片段中氧化剂的氧化作用。这个 第三个特定目标将调查金属、有机物质的影响 过氧化氢和一氧化氮对产物性质和分布的影响 由脱氧核苷、寡脱氧核苷酸和DNA片段形成。这个 拟议的研究将确定氧化剂特定DNA的标记产物 损害并提供更广泛的关于氧化剂在疾病中的作用的见解。

项目成果

Evaluation of N-hydroxy-2-thiopyridone as a nonmetal dependent source of the hydroxyl radical (HO.) in aqueous systems.

评估 N-羟基-2-硫代吡啶酮作为水性体系中羟基自由基 (HO.) 的非金属依赖性来源。

• DOI: 10.1016/0003-2697(92)90371-d
• 发表时间: 1992
• 期刊: Analytical biochemistry
• 影响因子: 2.9
• 作者: Hess,KM;Dix,TA
• 通讯作者: Dix,TA

Mechanism of site-selective DNA nicking by the hydrodioxyl (perhydroxyl) radical.

氢二氧基（过羟基）自由基对 DNA 进行位点选择性切口的机制。

• DOI: 10.1021/bi952010w
• 发表时间: 1996
• 期刊: Biochemistry.
• 作者: Dix,TA;Hess,KM;Medina,MA;Sullivan,RW;Tilly,SL;Webb,TL
• 通讯作者: Webb,TL

Effect of solution ionic strength on lipid peroxidation initiation by the perhydroxyl (xanthine oxidase-derived) and peroxyl radicals.

溶液离子强度对过羟基（黄嘌呤氧化酶衍生的）和过氧自由基引发脂质过氧化的影响。

• DOI: 10.1021/tx00026a018
• 发表时间: 1992
• 期刊: Chemical research in toxicology
• 影响因子: 4.1
• 作者: Aikens,J;Dix,TA
• 通讯作者: Dix,TA

Hydrodioxyl (perhydroxyl), peroxyl, and hydroxyl radical-initiated lipid peroxidation of large unilamellar vesicles (liposomes): comparative and mechanistic studies.

氢二氧基（过羟基）、过氧化氢和羟​​基自由基引发的大单层囊泡（脂质体）的脂质过氧化：比较和机制研究。

• DOI: 10.1006/abbi.1993.1455
• 发表时间: 1993
• 期刊: Archives of biochemistry and biophysics
• 影响因子: 3.9
• 作者: Aikens,J;Dix,TA
• 通讯作者: Dix,TA

Perhydroxyl radical (HOO.) initiated lipid peroxidation. The role of fatty acid hydroperoxides.

过羟基自由基（HOO.）引发脂质过氧化。

• 发表时间: 1991
• 期刊: The Journal of biological chemistry
• 作者: Aikens,J;Dix,TA
• 通讯作者: Dix,TA