SPECTROSCOPY OF CARCINOGEN DNA ADDUCTS

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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.