Simulation of DNA damage after proton irradiation

Area of Science:

• Biophysics
• Radiation Biology
• Computational Biology

Background:

• Accurate simulation of radiation-induced DNA damage is crucial for understanding biological effects.
• Proton therapy requires precise modeling of DNA double-strand breaks (DSBs) and fragmentations.
• Existing models need refinement to incorporate detailed biophysical interactions and DNA structures.

Purpose of the Study:

• To enhance the PARTRAC biophysical radiation track simulation model for proton interactions in water.
• To simulate DNA DSB induction and fragment size distributions following proton irradiation.
• To investigate the relationship between linear energy transfer (LET) and DNA damage complexity.

Main Methods:

• Improved PARTRAC model with new proton cross-section data for water.
• Superimposed simulated proton and electron tracks onto a detailed human genome DNA model.
• Simulated DSB induction across a range of LET values (1.6–70 keV/µm).

Main Results:

• DSB yield increased with LET, reaching ~20 DSBs/Gbp/Gy at higher LET, with a relative biological effectiveness (RBE) up to 2.2.
• Approximately half of the DSB increase was attributed to clustered damage in small DNA fragments (<10 kbp).
• Simulated fragment size distributions deviated from random breakage at LET >10 keV/µm, underestimating yields by up to 20% when using random breakage equations.

Conclusions:

• The enhanced PARTRAC model accurately reproduces trends in proton-induced DNA DSBs and fragmentation.
• LET is a critical factor influencing DSB yield, clustering, and fragment size distribution.
• Simulations highlight the importance of non-random DNA breakage patterns in assessing proton radiation damage.