Unlocking atom-specific radiotherapy - DNA backbone breakage caused by X-ray photoactivation

Area of Science:

• Radiochemistry
• Molecular Biophysics
• Radiation Oncology

Background:

• Radiotherapy efficacy can be limited by DNA damage resistance.
• Iodine's high atomic number suggests potential for enhanced radiation absorption.
• Understanding molecular fragmentation is key to optimizing radiation-induced damage.

Purpose of the Study:

• To investigate the fragmentation mechanisms of iodine-doped DNA oligonucleotides under tender X-ray irradiation.
• To determine how iodine doping influences DNA backbone breakage.
• To explore the potential of iodine photoactivation for enhancing radiotherapy.

Main Methods:

• Experimental analysis using mass spectroscopy to detect DNA fragments.
• Computational modeling with Born-Oppenheimer molecular dynamics simulations.
• Targeted X-ray irradiation above iodine's L-edge ionization energies.

Main Results:

• Iodine doping significantly increased DNA fragments associated with phosphate and sugar backbone breakage.
• Fragmentation occurred at distances far from the initial photoactivation site.
• Simulations confirmed the generation of numerous small fragments and reactive oxygen species.

Conclusions:

• Iodine doping effectively amplifies radiation-induced DNA damage through photoactivation.
• Enhanced fragmentation mechanisms contribute to increased therapeutic potential in cancer treatment.
• Findings support iodine incorporation as a strategy to improve radiotherapy outcomes.