Impact of ionizing radiation and low-energy electrons on DNA functionality: radioprotection and radiosensitization potential of natural products.

Ionizing radiation (IR) is a key cancer treatment, but its DNA-damaging effects, particularly double-strand breaks (DSBs) and clustered lesions, pose challenges for therapy. Clustered DNA lesions, often induced by low-energy electrons (LEEs), contribute significantly to genomic instability and repair resistance. Chemotherapeutic agents like cisplatin can enhance IR-induced damage, making tumor cells more susceptible. Emerging strategies in radiation oncology target DNA repair pathways, using inhibitors like poly(ADP-ribose) polymerase (PARP) to sensitize tumors to IR. Natural products, including polyphenols, flavonoids, and alkaloids, offer promising radioprotective effects by scavenging reactive oxygen species and enhancing DNA repair. These agents not only protect normal tissues but also increase tumor sensitivity to IR, improving therapeutic outcomes. Future research should focus on optimizing these natural agents for clinical use, integrating them into radiotherapy protocols for enhanced efficacy and reduced toxicity.