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Radiation-induced DNA radicals and DNA damage intermediates are highly reactive chemical species formed when ionizing radiation interacts with cellular DNA, either through direct ionization or indirectly via the radiolysis of water. These intermediates include base-centered radicals (such as the guanine cation radical), sugar-centered radicals, and various oxidative lesions like abasic sites and clustered damage. If these transient radicals are not neutralized, they can react with oxygen to form permanent, non-restorable lesions (the oxygen fixation hypothesis) or undergo chemical reactions leading to single-strand and lethal double-strand breaks. In clinical practice, these intermediates are the primary targets for radioprotective agents like amifostine, which scavenge free radicals and donate hydrogen atoms to chemically restore the DNA. Conversely, radiosensitizers aim to stabilize these radicals or exploit hypoxic environments to enhance the lethality of radiation in tumor cells. Understanding the kinetics and repair of these intermediates is fundamental to optimizing radiotherapy and developing countermeasures for radiation-induced toxicities.
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