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The elucidation of fundamental mechanisms underlying ion-induced radiationdamage of biological systems is crucial for the advancement of radiotherapywith ion beams and for radiation protection in space. The study of ion-inducedbiodamage using the phenomenon-based MultiScale Approach to the physics ofradiation damage with ions (MSA) has led to the prediction of nanoscale shockwaves (SW) that are created by ions in the biological medium at the high linearenergy transfer (LET). The high-LET regime corresponding to energy losseshigher than 1 keV/nm is typical for ions heavier than carbon in biologicalmedia at the Bragg peak region. This paper reveals that the thermomechanicalstress of the DNA molecule by the ion-induced SW becomes the dominant mechanismof complex DNA damage at the high-LET ion irradiation. Damage of the DNAmolecule in water caused by the ion-induced SW is studied by means of reactivemolecular dynamics simulations. Five projectile ions (C, O, Si, Ar, and Fe) atthe Bragg peak energies are considered. Simulations reveal that Ar and,especially, Fe ions induce multiple bond breakages in a DNA segment containing20 base pairs. The DNA damage produced in segments of such size leads tocomplex irreparable lesions in a cell. This makes the SW-inducedthermomechanical stress the dominant mechanism of complex DNA damage at thehigh-LET ion irradiation. A detailed theory for evaluating the DNA damagecaused 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 athigh-LET is sufficient to produce highly complex, lethal damages to a cell bythe SW-induced thermomechanical stress. A good agreement of the calculated cellsurvival probabilities with experimental data obtained for the cell irradiationwith iron ions provides strong experimental evidence of the ion-induced SWeffect.

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