Clustered DNA Damage Patterns after Proton Therapy Beam Irradiation Using Plasmid DNA

Area of Science:

• Radiation biology
• Biophysics
• Medical physics

Background:

• Understanding DNA damage mechanisms is crucial for proton cancer therapy.
• Proton therapy effectiveness relies on precise knowledge of radiation-induced DNA alterations.

Purpose of the Study:

• To measure irradiation-induced complex DNA damage in plasmid DNA exposed to protons.
• To investigate the influence of Linear Energy Transfer (LET) and Reactive Oxygen Species (ROS) on DNA fragmentation.

Main Methods:

• Plasmid pBR322 irradiation at MedAustron facility with energies 137-198 MeV.
• Agarose Gel Electrophoresis and Atomic Force Microscopy (AFM) for DNA damage assessment.
• Varying scavenger concentrations (Tris, C3CA) to modulate ROS levels.

Main Results:

• Quantified induction rates for single-strand breaks (SSBs), double-strand breaks (DSBs), base lesions, and non-DSB clusters.
• Demonstrated the significant roles of LET and ROS in DNA fragmentation.
• AFM revealed increasing DNA damage complexity with higher LET.

Conclusions:

• LET and ROS are key factors in proton-induced DNA fragmentation.
• AFM provides valuable insights into complex DNA damage induction by protons.
• Findings contribute to optimizing proton therapy protocols for cancer treatment.