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

Abstract

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 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.

Materials and methods

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.

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 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.

Conclusions

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.

Keywords:

• Iodine-125
• Auger emitters
• DNA damage
• radiation dosimetry
• Monte Carlo simulation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

MEAA acknowledges the financial support of the Site de Recherche Intégrée sur le Cancer de Bordeaux, Bordeaux Recherche Intégrée en Oncologie (SIRIC BRIO).

Notes on contributors

Mario Enrique Alcocer Ávila

Mario E. Alcocer Ávila earned a PhD in physics from Bordeaux University. He is currently a postdoctoral researcher at the University of Lyon. His research interests include radiation and computational physics.

Elif Hindié

Elif Hindié is Professor of Nuclear Medicine at Bordeaux University and Hospitals. He is a specialist in the use of radionuclides for imaging and therapy in oncology as well as in endocrine diseases.

Christophe Champion

Christophe Champion is Professor of Physics at Bordeaux University. His research activities consist in describing in detail the collisional mechanisms induced by charged particles in biological media. In this context, he developed various theoretical models to model the elastic and inelastic processes, all described within the quantum mechanical framework. In parallel, C. Champion has developed a series of Monte Carlo codes for describing the charged particle track structure, namely, EPOTRAN (an acronym for Electron and POsitron TRANsport in biological medium) devoted to electron and positron transport—with its extension CELLDOSE focused on microdosimetry of radionuclide emitters—and TILDA as well as its recent extension TILDA-V, devoted to ion transport in liquid water and DNA components, respectively.