How to explain the sensitivity of DNA double-strand breaks yield to 125I position?
International Journal of Radiation Biology. 2022-03-08; : 1-6
DOI: 10.1080/09553002.2022.2047822
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Author information:
(1)Université de Bordeaux-CNRS-CEA, Centre Lasers Intenses et Applications, UMR 5107, Talence, France.
(2)Université de Bordeaux, INCIA, CHU de Bordeaux – Service de Médecine Nucléaire, Pessac, France.
(3)Institut Universitaire de France (IUF), Paris, France.
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.