A Multiscale Kinetic Model of DNA Damage Signalling and Repair under Combined Proton and Nanoparticle Exposure
Abstract
We present a multiscale kinetic framework for predicting the induction, processing, and biological consequences of DNA double-strand breaks (DSBs) in AG1522 human fibroblasts exposed to combined proton and 15-nm GNP irradiation. The model connects proton dose and linear energy transfer (LET), perinuclear GNP localization, secondary-electron and reactive-species production, and Poisson--Gamma-distributed lesion induction. Initial DSBs are separated into simple and complex classes and coupled to an ATM--γH2AX--53BP1 signalling cascade, cell-cycle-dependent allocation among canonical non-homologous end joining, homologous recombination, alternative end joining, and single-strand annealing, and class-specific repair fidelities. The model identifies the initial complex-lesion fraction and its slower resolution, rather than post-irradiation conversion of simple DSBs, as the principal determinants of persistent damage under high-LET, GNP-enhanced irradiation. The residual-DSB results provide strong internal out-of-sample validation of the kinetic component. However, the opposing biases in correct repair and misrepair reveal an inconsistency between the class-specific fidelities and the supplied integrated-fidelity endpoint. These repair-fate predictions should therefore be regarded as model-constrained estimates pending independent measurements of correct-end joining, mutation, chromosome aberrations, and clonogenic survival.
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BibTeX
@misc{loan2026multiscale,
title = {{A Multiscale Kinetic Model of DNA Damage Signalling and Repair under Combined Proton and Nanoparticle Exposure}},
author = {Mushtaq Loan},
howpublished = {arXiv},
year = {2026},
month = oct,
doi = {10.48550/arxiv.2610.29157},
eprint = {2610.29157},
archivePrefix = {arXiv},
url = {https://arxiv.org/abs/2610.29157},
}
RIS
TY - UNPB
TI - A Multiscale Kinetic Model of DNA Damage Signalling and Repair under Combined Proton and Nanoparticle Exposure
AU - Mushtaq Loan
PY - 2026
DA - 2026/10/23
PB - arXiv
DO - 10.48550/arxiv.2610.29157
UR - https://arxiv.org/abs/2610.29157
AB - We present a multiscale kinetic framework for predicting the induction, processing, and biological consequences of DNA double-strand breaks (DSBs) in AG1522 human fibroblasts exposed to combined proton and 15-nm GNP irradiation. The model connects proton dose and linear energy transfer (LET), perinuclear GNP localization, secondary-electron and reactive-species production, and Poisson--Gamma-distributed lesion induction. Initial DSBs are separated into simple and complex classes and coupled to an ATM--γH2AX--53BP1 signalling cascade, cell-cycle-dependent allocation among canonical non-homologous end joining, homologous recombination, alternative end joining, and single-strand annealing, and class-specific repair fidelities. The model identifies the initial complex-lesion fraction and its slower resolution, rather than post-irradiation conversion of simple DSBs, as the principal determinants of persistent damage under high-LET, GNP-enhanced irradiation. The residual-DSB results provide strong internal out-of-sample validation of the kinetic component. However, the opposing biases in correct repair and misrepair reveal an inconsistency between the class-specific fidelities and the supplied integrated-fidelity endpoint. These repair-fate predictions should therefore be regarded as model-constrained estimates pending independent measurements of correct-end joining, mutation, chromosome aberrations, and clonogenic survival.
ER -