A biphasic spatiotemporal non-homologous end joining model coupled with Monte Carlo DNA damage data for chromosome aberration prediction.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	A biphasic spatiotemporal non-homologous end joining model coupled with Monte Carlo DNA damage data for chromosome aberration prediction.
Συγγραφείς:	Zhao M; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, People's Republic of China., Wu J; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, People's Republic of China., Huang G; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China., Zheng C; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, People's Republic of China., Huang X; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, People's Republic of China., Liang Y; National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen 518116, People's Republic of China.
Πηγή:	Physics in medicine and biology [Phys Med Biol] 2026 Sep 11; Vol. 71 (17). Date of Electronic Publication: 2026 Sep 11.
Τύπος έκδοσης:	Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: IOP Publishing Country of Publication: England NLM ID: 0401220 Publication Model: Electronic Cited Medium: Internet ISSN: 1361-6560 (Electronic) Linking ISSN: 00319155 NLM ISO Abbreviation: Phys Med Biol Subsets: MEDLINE
Imprint Name(s):	Original Publication: Bristol : IOP Publishing
Ιατρικοί όροι (MeSH):	Chromosome Aberrations/radiation effects , DNA End-Joining Repair/radiation effects , Monte Carlo Method* , DNA Damage*, Gamma Rays/adverse effects ; Fibroblasts/radiation effects ; Fibroblasts/metabolism ; Humans ; Time Factors ; Kinetics
Περίληψη:	Objective.This study extends a DNA damage simulation package to incorporate a biphasic spatiotemporal non-homologous end joining (NHEJ) repair framework. The aim is to predict radiation induced chromosome aberrations for various beam qualities and dose rates from an independent parameter set.Approach.A biphasic NHEJ kinetic model, characterized by fast and slow components with experimentally constrained repair rate constants (λf= 2.48 h^-1andλs= 0.408 h^-1) and slow portion (ηDSB= 19%), was coupled to a DNA end diffusion process (D= 0.1 μm²h^-1). DNA damage data from Monte Carlo-based biophysical program was used as input, while different types of chromosome aberrations were generated as output. The extended framework was benchmarked against chromosome aberration measurements in human fibroblasts under acuteγ-rays,αparticles, and chronic low dose-rateγ-ray irradiations. All parameters were obtained from independent measurements without fitting to chromosome aberration data. Model performance was evaluated using the coefficient of determination (R²).Main Results.For acuteγ-rays andαparticles, the proposed model reproduced the dose-response curves of dicentrics and interstitial deletions with reasonable accuracy, while larger deviations were observed for rings and terminal deletions. The corresponding total-aberrationR²were 0.973 and 0.947. Notably, the inclusion of spatiotemporal repair dynamics substantially improved agreement of rings and terminal deletions forα-particles compared to a pure distance-dependent model. Simulations of chronicγ-ray irradiations reproduced total aberration yields at 6.3 cGy h^-1withR²= 0.968, while the 2.8 cGy h^-1case exhibited notable deviation withR²= - 0.517. Sensitivity analyses suggested model stability and robustness with all sensitivity coefficients remaining below 1.3.Significance.By integrating spatial diffusion and biphasic repair kinetics, the proposed model provides a quantitative link between microdosimetric energy deposition and macroscopic chromosome aberrations. The approach offers a foundation for mechanistic modeling of relative biological effectiveness in particle therapy. (© 2026 Institute of Physics and Engineering in Medicine. All rights, including for text and data mining, AI training, and similar technologies, are reserved.)
Contributed Indexing:	Keywords: RBE model; biphasic NHEJ; chromosome aberration; particle therapy; spatiotemporal dynamics
Entry Date(s):	Date Created: 20260911 Date Completed: 20260911 Latest Revision: 20260911
Update Code:	20260911
DOI:	10.1088/1361-6560/ae95d8
PMID:	42723441
Βάση Δεδομένων:	MEDLINE

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