一种适用于长时间辐射条件下辐射诱导 DNA 损伤动力学和修复的空间量值模型。

A spatial measure-valued model for radiation-induced DNA damage kinetics and repair under protracted irradiation condition.

机构信息

University of Trento: Universita degli Studi di Trento, Trento, TN, Italy.

出版信息

J Math Biol. 2024 Jan 29;88(2):21. doi: 10.1007/s00285-024-02046-3.

Abstract

In the present work, we develop a general spatial stochastic model to describe the formation and repair of radiation-induced DNA damage. The model is described mathematically as a measure-valued particle-based stochastic system and extends in several directions the model developed in Cordoni et al. (Phys Rev E 103:012412, 2021; Int J Radiat Biol 1-16, 2022a; Radiat Res 197:218-232, 2022b). In this new spatial formulation, radiation-induced DNA damage in the cell nucleus can undergo different pathways to either repair or lead to cell inactivation. The main novelty of the work is to rigorously define a spatial model that considers the pairwise interaction of lesions and continuous protracted irradiation. The former is relevant from a biological point of view as clustered lesions are less likely to be repaired, leading to cell inactivation. The latter instead describes the effects of a continuous radiation field on biological tissue. We prove the existence and uniqueness of a solution to the above stochastic systems, characterizing its probabilistic properties. We further couple the model describing the biological system to a set of reaction-diffusion equations with random discontinuity that model the chemical environment. At last, we study the large system limit of the process. The developed model can be applied to different contexts, with radiotherapy and space radioprotection being the most relevant. Further, the biochemical system derived can play a crucial role in understanding an extremely promising novel radiotherapy treatment modality, named in the community FLASH radiotherapy, whose mechanism is today largely unknown.

摘要

在本工作中,我们开发了一个通用的空间随机模型来描述辐射诱导的 DNA 损伤的形成和修复。该模型在数学上被描述为一个基于测度值的粒子随机系统,并在几个方向上扩展了 Cordoni 等人开发的模型(Phys Rev E 103:012412, 2021; Int J Radiat Biol 1-16, 2022a; Radiat Res 197:218-232, 2022b)。在这个新的空间表述中,细胞核中的辐射诱导的 DNA 损伤可以通过不同的途径进行修复或导致细胞失活。这项工作的主要创新之处在于严格定义了一个空间模型,该模型考虑了损伤的成对相互作用和连续的延长照射。前者从生物学的角度来看是相关的,因为簇状损伤不太可能被修复,从而导致细胞失活。后者则描述了连续辐射场对生物组织的影响。我们证明了上述随机系统解的存在唯一性,并刻画了其概率性质。我们进一步将描述生物系统的模型与一组带有随机不连续性的反应扩散方程耦合,这些方程模拟了化学环境。最后,我们研究了过程的大系统极限。所开发的模型可以应用于不同的情境,其中放射治疗和空间辐射防护是最相关的。此外,所得到的生化系统可以在理解一种极具前景的新型放射治疗模式中发挥关键作用,该模式在业界被称为FLASH 放射治疗,其机制目前在很大程度上尚不清楚。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cdc/10824812/f1cf10f0ad03/285_2024_2046_Fig1_HTML.jpg

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