Radiosensitization by a modified nucleotide that produces DNA interstrand cross-links under hypoxic conditions

This paper describes the reactivity of a molecule that combines two desirable chemical processes into one molecule for the first time. Interstrand cross-links (ISCs) are an effective family of lesions produced by cytotoxic agents that target DNA. For instance, ISCs are the source of mitomycin C's cytotoxicity. Radiosensitizing agents are molecules that enhance DNA damage produced by ionizing radiation, especially under O2-deficient conditions. Phenyl selenide 1 is the first example of a modified nucleotide that can be incorporated in DNA by polymerases, which produces ISCs when DNA containing it is exposed to gamma-radiolysis under O2-deficient conditions. These experiments suggest that 1 could be useful as a novel type of radiosensitizing agent.