MODELING STUDIES ON DICENTRICS INDUCTION AFTER SUB-MICROMETER FOCUSED ION BEAM GRID IRRADIATION

Area of Science:

• Radiation biology
• Biophysics
• Computational biology

Background:

• DNA double-strand breaks (DSB) are critical lesions that can lead to chromosomal aberrations.
• The formation of chromosomal aberrations, such as dicentrics, is influenced by the spatial distribution and complexity of DSBs.
• Biophysical models are essential for understanding the mechanisms underlying radiation-induced DNA damage and its consequences.

Purpose of the Study:

• To refine the PARTRAC biophysical simulation tool for modeling DNA double-strand breaks (DSB) and chromosomal aberrations.
• To investigate the impact of spatial clustering of DNA damage on dicentric yields using experimental data.
• To validate the refined model's predictive power against experimental results for various radiation types.

Main Methods:

• Utilized the PARTRAC simulation tool to model non-homologous end joining and chromosomal aberration formation.
• Employed the ion microbeam SNAKE to deliver precisely controlled doses of protons, Li ions, and C ions to AL human-hamster hybrid cells.
• Separated the effects of DSB spatial distribution (focusing) and DSB complexity (linear energy transfer, LET) by varying ion types and delivery modes.

Main Results:

• The refined PARTRAC model successfully reproduced the LET-dependence of dicentric yields.
• The model accurately captured the impact of the spatial distribution (focusing effect) of DSBs on dicentric formation.
• Simulations aligned well with experimental data, including biphasic rejoining kinetics and benchmarked against photon irradiation yields.

Conclusions:

• The refined PARTRAC model provides a robust framework for simulating radiation-induced chromosomal aberrations.
• The study successfully disentangled the contributions of DSB clustering and LET to dicentric yields.
• The model's predictive accuracy supports its utility in radiobiology research and radiation protection applications.