According to the American Cancer Society, more than 600,000 new cases of skin malignancies will be diagnosed in the U.S. each year. These as well as aging and disorders in the immune system are examples of photooxidatiave modifications to genomic DNA as a result of exposure of living organisms to solar UV radiation. At the molecular level these deleterious effects have been explained in terms of photoinduced base lesions in the nucleic acids. There have been reports of purine photoproducts in UV irradiated DNA which could also lead to these deleterious effects. Stable products of the purine moieties of DNA or reactive intermediates participating in the photochemical processes have not been studied in the same detail as is the case of the pyrimidine bases. In this continuation proposal our main objectives are to: 1. Isolate and characterize the products in the photodestruction mechanism of purine derivatives. These will be correlated to their short lived intermediates already identified and compared to products formed during high intensity nanosecond laser irradiation. 2. Identify intermediates and characterize products in the purine photoinitiated cross-linking reactions with molecules considered to be models for the side chain of amino acids and with amino acids. 3. Study reactions of reactive free radicals produced by the UV photoionization of purines such as the radical cation and the radical anion with biomolecules and to establish their extent of participation in the photodegradation mechanism. All this information will help to understand the role of purines in the DNA photochemistry.
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