Lethal DNA damage caused by ion-induced shock waves in cells.

The elucidation of fundamental mechanisms underlying ion-induced radiation damage of biological systems is crucial for advancing radiotherapy with ion beams and for radiation protection in space. The study of ion-induced biodamage using the phenomenon-based multiscale approach (MSA) to the physics of radiation damage with ions has led to the prediction of nanoscale shock waves created by ions in a biological medium at the high linear energy transfer (LET). The high-LET regime corresponds to the keV and higher-energy losses by ions per nanometer, which is typical for ions heavier than carbon at the Bragg peak region in biological media. This paper reveals that the thermomechanical stress of the DNA molecule caused by the ion-induced shock wave becomes the dominant mechanism of complex DNA damage at the high-LET ion irradiation. Damage of the DNA molecule in water caused by a projectile-ion-induced shock wave is studied by means of reactive molecular dynamics simulations. Five projectile ions (carbon, oxygen, silicon, argon, and iron) at the Bragg peak energies are considered. For the chosen segment of the DNA molecule and the collision geometry, the number of DNA strand breaks is evaluated for each projectile ion as a function of the bond dissociation energy and the distance from the ion's path to the DNA strands. Simulations reveal that argon and especially iron ions induce the breakage of multiple bonds in a DNA double convolution containing 20 DNA base pairs. The DNA damage produced in segments of such size leads to complex irreparable lesions in a cell. This makes the shock-wave-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 shock-wave-induced thermomechanical stress. Accounting for the shock-wave-induced thermomechanical mechanism of DNA damage provides an explanation for the "overkill" effect observed experimentally in the dependence of cell survival probabilities on the radiation dose delivered with iron ions. This important observation provides strong experimental evidence of the ion-induced shock-wave effect and the related mechanism of radiation damage in cells.