Study of primary and secondary low-energy electron impacts on atomistic DNA strand breaks using Monte Carlo simulations.

Abstract

Purpose: In radiotherapy, the primary goal is to eliminate cancer cells while minimizing damage to healthy cells. The low-energy electrons generated by radiation beams interact with deoxyribonucleic acid (DNA), causing double-strand breaks that are challenging to repair, ultimately leading to tumor cell death, since the radiation provokes a clustered damage and the tumor cells have defective or dysregulated DNA repair pathways.

Methods: We performed Monte Carlo simulations using standard GEANT4 classes, employing an atomistic model of DNA composed of 1122 base pairs, with each atom represented by a sphere corresponding to its van der Waals radius. DNA samples were exposed to mono-energetic electrons between 1 and 30 eV. The simulations incorporated the cross-sections of DNA strands and bases, and we ran 10 million electrons for each simulation. Three types of electron interactions with their positions x, y, z within the DNA volume were recorded: dissociative electron attachment (DEA), excitation, and ionization. Using the number and type of interactions at the atomic level caused by primary and secondary electrons, the number of single (SSB) and double (DSB) strand breaks in DNA was determined based on energy-deposition thresholds.

Results: We found that at energies <10 eV, DEA plays a more dominant role in DNA strand breaks than excitation and ionization, which are effective only when the deposited energy exceeds 8.22 eV for excitation and 17.5 eV for ionization. We observed that the DNA side exposed to the incident electrons was more subject to electron interactions.

Conclusion: Our results show good agreement with experimental results in its global SSB and DSB, and our simulation accurately distinguished the breaks based on the type of interactions and the energy of the incident electrons. However, the absolute yields and the relative contribution of the different interaction types remain dependent on the modeled DNA geometry and irradiation conditions. Such a simulation reports DNA radiosensitivity at the atomic level and significantly contributes to the selection of radiopharmaceuticals targeting tumor cell nuclei such as those incorporating Auger electron emitters which are more effective than alpha and beta emitters.