How to explain the sensitivity of DNA double-strand breaks yield to I-125 position?

Purpose Auger emitters exhibit interesting features due to their emission of a cascade of short-range Auger electrons. Maximum DNA breakage efficacy is achieved when decays occur near DNA. Studies of double-strand breaks (DSBs) yields in plasmids revealed cutoff distances from DNA axis of 10.5 angstrom-12 angstrom, beyond which the mechanism of DSBs moves from direct to indirect effects, and the yield decreases rapidly. Some authors suggested that the average energy deposited in a DNA cylinder could explain such cutoffs. We aimed to study this hypothesis in further detail. Materials and methods Using the Monte Carlo code CELLDOSE, we investigated the influence of the I-125 atom position on energy deposits and absorbed doses per decay not only in a DNA cylinder, but also in individual strands, each modeled as 10 spheres encompassing the fragility sites for phosphodiester bond cleavage. Results The dose per decay decreased much more rapidly for a sphere in the proximal strand than for the DNA cylinder. For example, when moving the I-125 source from 10.5 angstrom to 11.5 angstrom, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder. Conclusions Explaining variations in DSBs yields with I-125 position should consider the probability of inducing damage in the proximal strand (nearest to the I-125 atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4 pi) emission of I-125 low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.