The Effects of Particle LET and Fluence on the Complexity and Frequency of Clustered DNA Damage.

Motivation: Clustered DNA-lesions are predominantly induced by ionizing radiation, particularly by high-LET particles, and considered as lethal damage. Quantification of this specific type of damage as a function of radiation parameters such as LET, dose rate, dose, and particle type can be informative for the prediction of biological outcome in radiobiological studies. This study investigated the induction and complexity of clustered DNA damage for three different types of particles at an LET range of 0.5-250 keV/μm. Methods: Nanometric volumes (36.0 nm Results: The total amount of DNA damage depends on particle type and LET. The number of ionization events underestimates the quantity of DNA damage at LETs higher than 10 keV/μm. Minimum LETs of 9.4 and 11.5 keV/μm are required to induce clustered damage by a single track of proton and alpha particles, respectively. For a given radiation dose, an increase in LET reduces the number of particle tracks, leading to more complex clustered DNA damage, but a smaller number of separated clustered damage sites. Conclusions: The dependency of the number and the complexity of clustered DNA damage on LET and fluence suggests that the quantification of this damage can be a useful method for the estimation of the biological effectiveness of radiation. These results also suggest that medium-LET particles are more appropriate for the treatment of bulk targets, whereas high-LET particles can be more effective for small targets.