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| - Efficient DNA Interstrand Cross-Link Formation from a Nucleotide Radical
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| - 5-(2‘-Deoxyuridinyl)methyl radical (1) is produced during γ-irradiation of DNA and other methods of oxidative stress. Independent generation of this reactive intermediate in duplex results in significant levels of DNA interstrand cross-links. Cross-link formation does not require O2 and involves reaction between the nucleotide where the radical is originally generated and the opposing deoxyadenosine. This is the first example in which formation of a nucleotide radical ultimately results in DNA−DNA cross-links. Interstrand DNA cross-links are difficult to repair and are believed to be the source of cytotoxicity of antitumor agents, such as mitomycin C. The efficient formation of DNA cross-links through 1 should provide the impetus for the design of DNA damaging agents that exploit this pathway.
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