  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.
