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• W2314777745 abstract "Reactive oxygen radicals have been implicated in diverse pathological processes (1) including the initiation and promotion phases of carcinogenesis (2-4), aging (5), and biological damage following ischemia (6). Two well recognized mechanisms for the production of oxidizing free radicals are via autoxidation processes and by ionizing radiation. It is of interest to compare the products resulting from these two modalities, particularly in relation to damage incurred by DNA constituents. This report describes the products obtained when a DNA model compound, namely 2'-deoxyadenylyl-(3'-5')-thymidine, d(ApT), is exposed to free radicals generated by autoxidizing compounds and by ionizing radiation. Figure 1 a shows the HPLC product profile obtained after d(ApT) was exposed in an oxygenated aqueous solution to ionizing radiation. The major products have been identified previously using NMR spectroscopy and mass spectrometry (7). Figure lb shows the HPLC product profile obtained after d(ApT) was exposed for 48 h at room temperature in an oxygenated aqueous solution to which ascorbic acid was added. Evidently the major products are the same in la and lb. The main product is a formamido modification which probably results from degradation of a precursor 5(6)-hydroxy-6(5)-hydroperoxy-5,6-dihydrothymine modification of d(ApT). Only a formamido fragment of the thymine base remains in this modification which has been described by Cadet et al. (8). Other major products include bases, mononucleotide, 5,6-dihydroxy-5,6-dihydrothymine (glycol) derivatives of d(ApT), and d(ApT) oxidized at the 5' end to give the aldehyde. Not only are the major products generated by the two modalities the same, but the distribution profiles are the same. Analogous results were obtained using 6-hydroxydopamine and dialuric acid as autoxidizing agents. The effect of various mediators on the product profile of d(ApT) obtained via autoxidation was examined to obtain insights into the molecular mechanisms involved. Superoxide dismutase reduced the amount of product somewhat, but the distribution of products appeared unchanged. Catalase, on the other hand, completely inhibited product formation. This result shows clearly that hydrogen peroxide plays a role. It was of interest to determine whether trace amounts of metal complexes could be" @default.
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• W2314777745 date "1987-10-01" @default.
• W2314777745 modified "2023-09-25" @default.
• W2314777745 title "Comparison of Free Radical Damage in Dinucleoside Monophosphate via Autoxidation Processes and by Ionizing Radiation" @default.
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• W2314777745 doi "https://doi.org/10.2307/3577089" @default.
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