Cellular DNA and associated macromolecules (DNA)

Cellular DNA and its associated macromolecules, such as histones and the broader chromatin structure, serve as the primary biological targets for ionizing radiation during total body irradiation (TBI). TBI is a medical procedure used primarily as a conditioning regimen for hematopoietic stem cell transplantation to eradicate malignant cells and induce systemic immunosuppression (StatPearls, 2023). The mechanism of action involves the induction of complex DNA damage, including single-strand and double-strand breaks, through both direct ionization and the generation of reactive oxygen species (Hall & Giaccia, 2018). This damage triggers the DNA damage response, leading to cell cycle arrest, senescence, or apoptosis, particularly in rapidly dividing hematopoietic and neoplastic cells (PubMed, 2022). While effective for cytoreduction, the non-specific nature of DNA damage across the entire body presents significant therapeutic challenges, including the risk of acute radiation syndrome and long-term complications like secondary malignancies or organ dysfunction (NIH, 2022). Consequently, TBI is often carefully dosed and sometimes combined with DNA-targeting drugs like cyclophosphamide to optimize the therapeutic index (NCBI, 2020).

Other names

Deoxyribonucleic acidGenomic DNANuclear DNAChromatinTotal body irradiation target

Ionizing radiation causes DNA damage through direct ionization of the phosphodiester backbone or indirect action via water radiolysis, creating hydroxyl radicals that induce oxidative damage. The resulting double-strand breaks (DSBs) are the primary lethal lesions, activating the ATM/ATR signaling pathways and p53-mediated apoptosis (Hall & Giaccia, 2018; PubMed, 2022).