A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields

Area of Science:

• Radiation biology
• DNA damage
• Computational modeling

Background:

• Complex DNA damage, involving multiple lesions, is critical for human tissue damage after radiation exposure.
• Directly measuring nanoscale DNA damage aggregation is challenging, necessitating simulation and experimental approaches.
• Monte Carlo simulations of radiation track structure in water are commonly used to evaluate DNA damage.

Purpose of the Study:

• To propose a simplified cluster analysis for estimating complex DNA damage yields from electron and X-ray irradiations.
• To compare computational results with experimental data for complex DNA damage, including base damage (BD).
• To quantify complex DNA damage types not measurable by in vitro experiments.

Main Methods:

• Developed a simplified cluster analysis of ionization and electronic excitation events within 10 bp.
• Used track structure-based simulation for electron and X-ray irradiations.
• Compared simulation results with experimental complex DNA damage data (SSBs, DSBs, complex BD) measured by enzymatic cleavage and AFM.

Main Results:

• Computational results closely matched experimental fractions of complex DNA damage yields when BD/SSB ratio was 1.3.
• The aggregation of events along electron tracks correlates with DNA damage complexity.
• 43.5% of double-strand breaks (DSBs) from 70 kVp X-ray irradiation were classified as complex, involving base damage (BD).

Conclusions:

• The simplified simulation model effectively estimates complex DNA damage yields for electron and X-ray exposures.
• The model quantifies complex damage types and aids in interpreting experimental detection efficiencies.
• This approach enhances the precise understanding of DNA damage complexity induced by radiation.