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

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 Å-12 Å, 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.

Using the Monte Carlo code CELLDOSE, we investigated the influence of the ¹²⁵I 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.

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 ¹²⁵I source from 10.5 Å to 11.5 Å, the average dose to the sphere dropped by 43%, compared to only 13% in the case of the cylinder.

Explaining variations in DSBs yields with ¹²⁵I position should consider the probability of inducing damage in the proximal strand (nearest to the ¹²⁵I atom). The energy received by fragility sites in this strand is highly influenced by the isotropic (4π) emission of ¹²⁵I low-energy Auger electrons. The positioning of Auger emitters for targeted radionuclide therapy can be envisioned accordingly.