Multinomial probability model of radiation induced DSB and non-DSB clusters: tandem and bistranded damage clusters

Experiments have shown that non-double strand break (DSB) clustered damage consisting of two or more base damages (BDs) or BD with single strand breaks (SSBs) occur with higher frequency than DSBs after ionizing radiation exposure. However experiments that measure tandem non-DSB clusters have not been developed. I develop a probability model of clustered damage that is combined with energy imparted spectra to predict the relative contributions of tandem and bistranded non-DSB clustered damage. The model considers probabilities for direct damage to sugar-phosphate moieties leading to SSBs, direct damage to DNA bases leading to abasic or oxidized sites, and indirect damage leading to radical formation with subsequent SSB and BD formation. Additional probabilities account for relative location of SSB and BD to model damage clusters. The model predicts for electrons and ions the relative contribution of tandem or bistranded lesions, the larger occurrence of clustered non-DSBs compared to DSBs, and the predominance of mixtures of damage types. Predictions of ratios of non-DSB clusters to DSB of 4-to-6 are found for electrons and high energy ions. The model provides an accurate method to predict DSB and non-DSB damage clusters as a function of radiation modality and to model resulting damage processing.