{"title":"How to explain the sensitivity of DNA double-strand breaks yield to 125I position?","authors":"Mario Enrique Alcocer ÁvilaCELIA, IP2I Lyon, Elif HindiéIUF, INCIA, Christophe ChampionCELIA","doi":"arxiv-2409.11185","DOIUrl":null,"url":null,"abstract":"Purpose: Auger emitters exhibit interesting features due to their emission of\na cascade of short-range Auger electrons. Maximum DNA breakage efficacy is\nachieved when decays occur near DNA. Studies of double-strand breaks (DSBs)\nyields in plasmids revealed cutoff distances from DNA axis of 10.5-12 {\\AA},\nbeyond which the mechanism of DSBs moves from direct to indirect effects, and\nthe yield decreases rapidly. Some authors suggested that the average energy\ndeposited in a DNA cylinder could explain such cutoffs. We aimed to study this\nhypothesis in further detail.Materials and methods: Using the Monte Carlo code\nCELLDOSE, we investigated the influence of the 125I atom position on energy\ndeposits and absorbed doses per decay not only in a DNA cylinder, but also in\nindividual strands, each modeled as 10 spheres encompassing the fragility sites\nfor phosphodiester bond cleavage.Results: The dose per decay decreased much\nmore rapidly for a sphere in the proximal strand than for the DNA cylinder. For\nexample, when moving the 125I source from 10.5 {\\AA} to 11.5 {\\AA}, the average\ndose to the sphere dropped by 43%, compared to only 13% in the case of the\ncylinder.Conclusions: Explaining variations in DSBs yields with 125I position\nshould consider the probability of inducing damage in the proximal strand\n(nearest to the 125I atom). The energy received by fragility sites in this\nstrand is highly influenced by the isotropic (4$\\pi$) emission of 125I\nlow-energy Auger electrons. The positioning of Auger emitters for targeted\nradionuclide therapy can be envisioned accordingly.","PeriodicalId":501022,"journal":{"name":"arXiv - QuanBio - Biomolecules","volume":"175 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"arXiv - QuanBio - Biomolecules","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/arxiv-2409.11185","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
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 10.5-12 {\AA},
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 {\AA} to 11.5 {\AA}, 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 (4$\pi$) emission of 125I
low-energy Auger electrons. The positioning of Auger emitters for targeted
radionuclide therapy can be envisioned accordingly.