SPECTROSCOPY OF CARCINOGEN DNA ADDUCTS

描述：劳伦斯·W·约翰逊博士是约克大学的化学教授 大学，城市大学，并在高分辨率方面有广泛的背景 卟啉的电子能谱研究。由于接触到了两个 作为生物学教授，约翰逊博士对DNA越来越感兴趣。 作为改变他的研究的第一步，约翰逊博士花了一个 与纽约大学的Geacintov教授一起休假，研究 碱基序列和溶剂对共价结合荧光寿命的影响 Benzo[a]pyrene-7，8-diol-9，10-epoxide-oligonucleotide加合物。这是一次 非常有教育意义的经验，但首席调查员认为他可能 能够通过更多有指导的研究为这一领域的研究做出贡献。 Geacintov教授有一个庞大且非常活跃的小组；他与 纽约大学和世界各地的许多其他教职员工。如果这个奖项 一旦获得资金，这项工作的扩展将会发生。最近，高分辨率 核磁共振技术为加合物的结构提供了新的细节 当对环境重要的致癌代谢物 7，8-二氢二醇-9，10-环氧苯并[a]芘(BPDE)立体异构体结合 与DNA共价并导致突变。已有研究表明，BPDE-DNA 可以从一种构象转换为另一种构象的损伤可能是 在诱变热点现象中尤为重要。法律的有效性 这一假设将使用构象敏感的 特定部位的吡喃基残基的荧光衰变曲线 BPDE-作为工具的寡核苷酸加合物。长期目标是 确定多环芳烃的碱基序列和立体化学性质 二醇环氧化物-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。 短期目标是完成他在DNA研究方面的学徒生涯。这个 长期目标是继续与Geacintov教授合作， 也是为了与生物学领域的同事建立合作关系，他们也是 对DNA感兴趣。

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.