DNA Damage Induced by Ionizing Radiation (IR-DNA Damage)

DNA Damage Induced by Ionizing Radiation Overview

Ionizing radiation is a cancer therapy that targets tumor cells by inducing DNA damage, primarily double-strand breaks (DSBs). The damage arises from direct interaction of radiation with DNA or indirectly via reactive oxygen species (ROS) generated by the radiation. Cells respond via the DNA Damage Response (DDR), leading to cell cycle arrest, repair, apoptosis, or senescence. Surviving cells can exhibit genomic instability. Radiation induces immunogenic cell death. Therapeutic strategies involve radiosensitizers that inhibit DDR components to enhance tumor kill. Safety concerns include damage to normal tissues and secondary malignancies.

Mechanism of Action

Ionizing radiation induces DNA damage primarily through the generation of double-strand breaks (DSBs), single-strand breaks (SSBs), base modifications, and DNA crosslinks via direct bond cleavage and indirect action through reactive oxygen species (ROS). This activates the DNA Damage Response (DDR) pathways, leading to cell cycle arrest, DNA repair, and ultimately, apoptosis, mitotic catastrophe, senescence, or genomic instability if repair fails. The immunogenic cell death pathway is also activated to promote immune recognition and clearance of damaged tumor cells.

Biological Functions

Safety Considerations

Interacting Drugs

Associated Biomarkers