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How do free radicals produced by radiation damage cellular DNA?

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linear accelerator; external beam radiation therapy — radiation therapy External beam radiation therapy (also known as external beam teletherapy, or long-distance therapy) being delivered using a machine known as a linear accelerator.

In the context of radiation therapy, ionizing radiation damages cellular DNA by creating free radicals within the cell. These highly reactive species are often produced when radiation cleaves water molecules into hydrogen atoms and hydroxyl radicals.12

These free radicals damage DNA primarily through the oxidation of bases, particularly guanine. This chemical modification can lead to mutations, such as G-T transversions, which are among the most common mutations associated with human cancer.1

Beyond base oxidation, ionizing radiation—both directly and through the action of these radicals—can cause structural damage to the DNA molecule, including single-strand and double-strand breaks. While cells possess sophisticated DNA repair mechanisms to address such lesions, unrepaired or misrepaired damage can prevent successful replication, ultimately leading to cell death. This process is the fundamental mechanism by which radiation therapy inhibits the replication of cancer cells and slows the progression of malignant disease.314