Abstract / Summary
Exposure to ionizing radiation initiates a rapid and highly coordinated cascade of physicochemical and biological events that ultimately determine cellular and systemic outcomes. This review provides an integrated analysis of the chemical, biochemical, and clinical consequences of ionizing radiation. At the molecular level, radiation induces ionization and excitation within femtoseconds, leading predominantly to water radiolysis and the generation of reactive oxygen species, particularly hydroxyl radicals, which are key mediators of oxidative damage. These reactive intermediates target critical macromolecules, with DNA representing the principal site of injury. Among DNA lesions, double-strand breaks are the most deleterious, as their misrepair can result in genomic instability and carcinogenesis. Subsequent activation of cellular defense mechanisms, including the DNA damage response and redox-sensitive signaling pathways, determines cell fate, ranging from successful repair and survival to apoptosis, senescence, or mitotic catastrophe. Beyond DNA, radiation-induced lipid peroxidation and protein oxidation disrupt membrane integrity, enzymatic function, and mitochondrial homeostasis, amplifying cellular dysfunction. At the tissue and organismal levels, these molecular events translate into two major categories of biological effects: deterministic effects, which exhibit dose-dependent thresholds and predictable severity, and stochastic effects, primarily cancer induction, are modeled without a defined threshold within the linear no-threshold protection framework, with risk increasing in probability with dose. Understanding these multiscale interactions is essential for optimizing radiotherapy strategies and reinforcing radiation protection principles, including justification, optimization, and dose limitation, to minimize both acute and long-term health risks.