<strong></strong>Modeling Clustered DNA Damage By Ionizing Radiation Using Multinomial Damage Probabilities And Energy Imparted Spectra

Simple and complex clustered DNA damage represent critical initial damage caused by radiation. In this paper a multinomial probability model of clustered damage is developed with probabilities dependent on the energy imparted to DNA and surrounding water molecules. The model consists of four probabilities: A) direct damage of sugar-phosphate moieties leading to SSB, B) OH- radical formation with subsequent SSB and BD formation, C) direct damage to DNA bases, and D) energy imparted to histone proteins and other molecules in a volume not leading to SSB or BD. These probabilities are augmented by introducing probabilities for relative location of SSB using a &lt;10 bp criteria for double strand break (DSB), and for the possible success of radical attack to lead to SSB or BD. Model predictions for electrons, 4He and 12C ions are compared to experimental data and show good agreement. Thus, the developed model allows an accurate and rapid computational method to predict simple and complex clustered DNA damage as a function of radiation quality and to explore the resulting challenges to DNA repair.