Lethal DNA damages caused by ion-induced shock waves in cells

TL;DR

This paper demonstrates that ion-induced shock waves cause complex, lethal DNA damage at high linear energy transfer, with simulations and theory showing the dominant role of thermomechanical stress in radiation damage.

Contribution

It introduces a new understanding of ion-induced DNA damage mechanism via shock waves and integrates this into the MultiScale Approach for radiation damage prediction.

Findings

Shock waves cause complex DNA damage at high-LET.

Simulations show Fe ions induce multiple bond breakages.

Theoretical model aligns with experimental cell survival data.

Abstract

The elucidation of fundamental mechanisms underlying ion-induced radiation damage of biological systems is crucial for the advancement of radiotherapy with ion beams and for radiation protection in space. The study of ion-induced biodamage using the phenomenon-based MultiScale Approach to the physics of radiation damage with ions (MSA) has led to the prediction of nanoscale shock waves (SW) that are created by ions in the biological medium at the high linear energy transfer (LET). The high-LET regime corresponding to energy losses higher than 1 keV/nm is typical for ions heavier than carbon in biological media at the Bragg peak region. This paper reveals that the thermomechanical stress of the DNA molecule by the ion-induced SW becomes the dominant mechanism of complex DNA damage at the high-LET ion irradiation. Damage of the DNA molecule in water caused by the ion-induced SW is studied by means of reactive molecular dynamics simulations. Five projectile ions (C, O, Si, Ar, and Fe) at the Bragg peak energies are considered. Simulations reveal that Ar and, especially, Fe ions induce multiple bond breakages in a DNA segment containing 20 base pairs. The DNA damage produced in segments of such size leads to complex irreparable lesions in a cell. This makes the SW-induced thermomechanical stress the dominant mechanism of complex DNA damage at the high-LET ion irradiation. A detailed theory for evaluating the DNA damage caused by ions at high-LET is formulated and integrated into the MSA formalism. The theoretical analysis reveals that a single ion hitting a cell nucleus at high-LET is sufficient to produce highly complex, lethal damages to a cell by the SW-induced thermomechanical stress. A good agreement of the calculated cell survival probabilities with experimental data obtained for the cell irradiation with iron ions provides strong experimental evidence of the ion-induced SW effect.