DNA radicals and other macromolecular radicals

DNA radicals and other macromolecular radicals are highly reactive chemical intermediates formed when biological polymers such as DNA, proteins, or lipids lose or gain electrons, typically due to ionizing radiation or oxidative stress (Cadet & Wagner, 2013). These radicals are central to the pathophysiology of radiation-induced tissue damage and the mechanism of action of certain cytotoxic drugs like bleomycin, which generate DNA-centered radicals to induce lethal strand breaks (PubChem, 2024). Conversely, they serve as the primary therapeutic targets for radioprotective agents like amifostine, which scavenge these reactive species to prevent irreversible cellular damage in healthy tissues. The accumulation of these radicals leads to permanent structural alterations, resulting in mutations, loss of protein function, or membrane disruption, which are hallmarks of aging and various chronic diseases (NCBI, 2023). In clinical oncology, managing the balance of these radicals is crucial, as they are both the mediators of therapeutic cell killing and the primary cause of off-target toxicity. Understanding the kinetics of radical formation and quenching is essential for the development of novel antioxidants and the optimization of radiotherapy protocols (PubMed, 2023).

Other names

DNA-centered radicalsMacromolecular free radicalsProtein radicalsLipid radicalsOxidative damage intermediatesBiopolymer radicals

Drugs targeting these species typically act through radical scavenging, where the drug neutralizes the radical by donating an electron or hydrogen atom, or through chemical repair of the macromolecule to prevent permanent strand breaks or cross-linking (NCBI, 2023).