SPECTROSCOPY OF CARCINOGEN DNA ADDUCTS

致癌物 DNA 加合物的光谱学

• 批准号: 2398104
• 负责人: LAWRENCE William JOHNSON
• 金额: $ 3.67万
• 依托单位: YORK COLLEGE
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2398104
• 关键词: DNA; DNA damage; adduct; benzopyrenediol epoxide; carbopolycyclic compound; chemical structure function; fluorescence; high performance liquid chromatography; mutagens; nuclear magnetic resonance spectroscopy; nucleic acid sequence; oligonucleotides

DESCRIPTION: Dr. Lawrence W. Johnson is a professor of chemistry at York College, CUNY, and has extensive background in the high resolution electronic spectroscopy of porphyrins. As a result of contact with two biology professors, Dr. Johnson has become increasingly interested in DNA. As a first step to making a change in his research, Dr. Johnson spent a sabbatical leave with Professor Geacintov at NYU studying the effects of base sequences and solvent on the fluorescence lifetimes of covalently bound benzo[a]pyrene-7,8-diol-9,10-epoxide-oligonucleotide adducts. This was a very educational experience, but the principal investigator believes he may be able to contribute to this area of research with more mentored research. Professor Geacintov has a large and very active group; he collaborates with numerous other faculty members at NYU and around the world. If this award is funded, an expansion of this work will occur. Recently, high resolution NMR techniques have provided new details about how the structures of adducts that arise when the environmentally important, tumorigenic metabolites of 7,8-dihydrodiol-9,10-epoxy-benzo[a]pyrene (BPDE) stereoisomers bind covalently to DNA and cause mutations. It has been suggested that BPDE-DNA lesions that can interconvert from one conformer to another may be particularly important in mutagenesis hotspot phenomena. The validity of this hypothesis will be investigated using the conformationally sensitive fluorescence decay profiles of the pyrenyl residues in site-specific BPDE-oligonucleotide adducts as a tool. The long range objectives are to determine how base sequence and the stereochemical properties of the PAH diol epoxide-DNA adducts influence the structure and function of DNA, and account for the stereoselective mutational characteristics of these lesions. The short term goal is to finish his apprenticeship in DNA research. The long term goals are to continue collaborating with Professor Geacintov and also to build a collaboration with colleagues in biology who are also interested in DNA.

描述：劳伦斯·W·约翰逊博士是约克化学教授 大学，CUNY，在高分辨率方面具有广泛的背景 卟啉的电子光谱。 由于与两个接触 生物学教授，约翰逊博士对DNA越来越感兴趣。 作为改变研究的第一步，约翰逊博士花了一个 与Geacintov教授一起休假，纽约大学研究的影响 基础序列和溶剂在共价结合的荧光寿命上 苯并[A] pyrene-7,8-二醇-9,10-环氧化物 - 寡核苷酸加合物。 这是一个 非常有教育意义的经验，但主要调查员认为他可能 能够通过更多的指导研究为这一研究领域做出贡献。 Gecintov教授有一个非常活跃的群体。他与之合作 纽约大学和世界各地的许多其他教职员工。 如果这个奖项 被资助，这项工作的扩展将发生。 最近，高分辨率 NMR技术提供了有关加合物结构的新细节 当环境重要的，肿瘤的代谢产物 7,8-二氢二醇-9,10-蛋白 - 苯并[a] pyrene（bpde）立体异构体结合 共价为DNA并引起突变。 有人建议BPDE-DNA 可以从一种构象异构体相互转化的病变可能是 在诱变热点现象中尤为重要。 的有效性 该假设将使用构象敏感 位点特异性中牙肾上腺残基的荧光衰减曲线 BPDE-寡核苷酸加合物作为工具。 远程目标是 确定PAH的基础序列和立体化学特性 二醇环氧-DNA加合物影响DNA的结构和功能， 解释了这些病变的立体选择性突变特征。 短期目标是完成他的DNA研究学徒制。 这 长期目标是继续与Gecintov教授合作 还与生物学同事建立合作 对DNA感兴趣。