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Numerical insight into the Dual Radiation Action Theory.

John J Tello1, Sébastien Incerti2, Ziad Francis3

  • 1Instituto de Física "Gleb Wataghin", Universidade Estadual de Campinas, Brazil; University of Pavia, Physics Department, via Bassi 6, I-27100 Pavia, Italy; INFN-Sezione di Pavia, via Bassi 6, I-27100 Pavia, Italy.

Physica Medica : PM : an International Journal Devoted to the Applications of Physics to Medicine and Biology : Official Journal of the Italian Association of Biomedical Physics (AIFB)
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Summary

This study numerically investigates DNA damage mechanisms from proton and alpha particle radiation using the Dual Radiation Action Theory (DRAT). Findings reveal how radiation dose influences lethal lesions and RBE, aligning with experimental data for heavy particles.

Keywords:
Alpha particlesDual Radiation Action TheoryMonte CarloProtonRadiobiology

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Area of Science:

  • Radiation biology
  • Biophysics
  • Nuclear physics

Background:

  • Understanding DNA damage mechanisms is crucial for radiation protection and therapy.
  • The Dual Radiation Action Theory (DRAT) describes radiation-induced cell killing based on one- and two-track events.
  • Heavy charged particles like protons and alpha particles present unique radiobiological challenges due to their high linear energy transfer (LET).

Purpose of the Study:

  • To numerically investigate the first and second-order mechanisms of lethal DNA lesion induction by protons and alpha particles.
  • To validate the Dual Radiation Action Theory (DRAT) for heavy charged particles using a detailed atomic-resolution model of genetic material.
  • To determine the dose-dependent relationship between radiation type, DNA damage, and biological effectiveness.

Main Methods:

  • Utilized a high-resolution geometrical model of genetic material (5.47 × 10^9 base pairs) up to the chromatin level.
  • Employed the GEANT4-DNA Monte Carlo code to simulate ion interactions with the DNA model.
  • Quantified lethal lesions from one- and two-track mechanisms and estimated the alpha/beta ratio and relative biological effectiveness (RBE).

Main Results:

  • The number of lethal lesions followed dose and squared dose dependencies, consistent with DRAT predictions.
  • Estimated RBE values aligned with experimental results for LET below approximately 100 keV/μm.
  • Observed an increase in the beta parameter with LET, leading to an increasing alpha/beta ratio, and explained the saturation of the alpha parameter at higher doses (> 6 Gy).

Conclusions:

  • The study provides numerical insights into DRAT mechanisms for heavy particles, linking physical parameters to biological outcomes.
  • The alpha parameter in cellular survival curves is influenced by physical alpha and beta parameters and specific energy deposition per track.
  • Findings contribute to a better understanding of radiation-induced DNA damage and its biological consequences, particularly for proton and alpha particle therapy applications.