A novel multitarget model of radiation-induced cell killing based on the Gaussian distribution

Zhao, Lei; Mi, Dong; Sun, Yeqing

doi:10.1016/j.jtbi.2017.03.002

Cited by 10 publications

(5 citation statements)

References 51 publications

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“…The main applications of such models are radiotherapy and space radioprotection. Although a plethora of mathematical models has been proposed over the years (Albright 1989;Bellinzona et al 2021;Curtis 1986;Thomas Friedrich et al 2012;Hawkins 1994Hawkins , 2003Hawkins , 2018Inaniwa et al 2013;Kase et al 2006;Kellerer and Rossi 1978;McMahon 2018;Nomiya 2013;Rossi and Zaider 1988;Sato and Furusawa 2012;Scholz et al 1997;Tobias 1980Tobias , 1985Vassiliev 2012;Zhao et al 2015Zhao et al , 2015Zhao, Mi, and Sun 2017), providing several mechanistic insights and successful predictive power in some cases, a rigorous analysis of the probabilistic setting of the model themselves is often missing. In particular, special attention on the assumed probability distributions for the driving processes and how much they reflect into the prediction of the cell-survival curves, is of interest to understand the range of validity of each model.…”

Section: Introductionmentioning

confidence: 99%

Multiple levels of stochasticity accounted for in different radiation biophysical models: from physics to biology

Cordoni

Missiaggia

Tessa

et al. 2022

International Journal of Radiation Biology

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Purpose: in the present paper we investigate how some stochastic effects are included in a class of radiobiological models with particular emphasis on how such randomnesses reflect into the predicted cell survival curve.Materials and Methods: we consider four different models, namely the Generalized Stochastic Microdosimetric Model GSM 2 , in its original full form, the Dirac GSM 2 , the Poisson GSM 2 and the Repair-Misrepair Model (RMR). While GSM 2 and the RMR models are known in literature, the Dirac and the Poisson GSM 2 have been newly introduced in this work. We further numerically investigate via Monte Carlo simulation of four different particle beams, how the proposed stochastic approximations reflect into the predicted survival curves. To achieve these results, we consider different ion species at energies of interest for therapeutic applications, also including a mixed field scenario.Results: we show how the Dirac GSM 2 , the Poisson GSM 2 and the RMR can be obtained from the GSM 2 under suitable approximations on the stochasticity considered. We analytically derive the cell survival curve predicted by the four models, characterizing rigorously the high and low dose limits. We further study how the theoretical findings emerge also using Monte Carlo numerical simulations.Conclusions: we show how different models include different levels of stochasticity in the description of cellular response to radiation. This translates into different cell survival predictions depending on the radiation quality.

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Section: Introductionmentioning

confidence: 99%

Multiple levels of stochasticity accounted for in different radiation biophysical models: from physics to biology

Cordoni

Missiaggia

Tessa

et al. 2022

International Journal of Radiation Biology

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“…This has been already noted in previous research [ 10 , 19 ]. Secondly, the incorporation of a Gaussian distribution, previously employed in radiobiology studies [ 24 , 25 ], emerges as a deviation from a Poisson distribution. As a result, the proposed model establishes a remarkably insightful link between two seemingly different radiobiological models: the MKM and the Gaussian formulation of a multi-hit model.…”

Section: Discussionmentioning

confidence: 99%

“…Lastly, it is worth stressing that the present paper sheds light on another possible future connection to existing radiobiological models. In fact, in the literature, some models have been derived that attempt to describe DNA damage at high doses using a Gaussian formulation of a multi-hit model (MHM) [ 24 , 25 ]. It has already been shown in [ 19 ] that GSM

is closely connected to some multi-hit models [ 26 , 27 ], so the results derived in the present paper further connect GSM

to the multi-hit models derived in the literature.…”

Section: Introductionmentioning

confidence: 99%

On the Emergence of the Deviation from a Poisson Law in Stochastic Mathematical Models for Radiation-Induced DNA Damage: A System Size Expansion

Cordoni

2023

Entropy

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In this paper, we study the system size expansion of a stochastic model for radiation-induced DNA damage kinetics and repair. In particular, we characterize both the macroscopic deterministic limit and the fluctuation around it. We further show that such fluctuations are Gaussian-distributed. In deriving such results, we provide further insights into the relationship between stochastic and deterministic mathematical models for radiation-induced DNA damage repair. Specifically, we demonstrate how the governing deterministic equations commonly employed in the field arise naturally within the stochastic framework as a macroscopic limit. Additionally, by examining the fluctuations around this macroscopic limit, we uncover deviations from a Poissonian behavior driven by interactions and clustering among DNA damages. Although such behaviors have been empirically observed, our derived results represent the first rigorous derivation that incorporates these deviations from a Poissonian distribution within a mathematical model, eliminating the need for specific ad hoc corrections.

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“…Contribute to Repair Pathway Choices. IR-induced DNA DSBs can occur in irradiated cells due to the direct effects through the energy deposition of IR [44][45][46], or the indirect effects through the generation of oxygen and nitrogen species (ROS and RNS) from the interaction of IR with water and molecules, and the leakage of mitochondrial dysfunctions [47] (Figure 2). Recently, studies in the field indicate that IR-induced DNA DSBs are mainly determined by radiation quality [48,49].…”

Section: The Type and Distribution Of Ir-induced Dsbsmentioning

confidence: 99%

The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks

Zhao

Bao

Shang

et al. 2020

BioMed Research International

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Ionising radiation- (IR-) induced DNA double-strand breaks (DSBs) are considered to be the deleterious DNA lesions that pose a serious threat to genomic stability. The major DNA repair pathways, including classical nonhomologous end joining, homologous recombination, single-strand annealing, and alternative end joining, play critical roles in countering and eliciting IR-induced DSBs to ensure genome integrity. If the IR-induced DNA DSBs are not repaired correctly, the residual or incorrectly repaired DSBs can result in genomic instability that is associated with certain human diseases. Although many efforts have been made in investigating the major mechanisms of IR-induced DNA DSB repair, it is still unclear what determines the choices of IR-induced DNA DSB repair pathways. In this review, we discuss how the mechanisms of IR-induced DSB repair pathway choices can operate in irradiated cells. We first briefly describe the main mechanisms of the major DNA DSB repair pathways and the related key repair proteins. Based on our understanding of the characteristics of IR-induced DNA DSBs and the regulatory mechanisms of DSB repair pathways in irradiated cells and recent advances in this field, We then highlight the main factors and associated challenges to determine the IR-induced DSB repair pathway choices. We conclude that the type and distribution of IR-induced DSBs, chromatin state, DNA-end structure, and DNA-end resection are the main determinants of the choice of the IR-induced DNA DSB repair pathway.

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A novel multitarget model of radiation-induced cell killing based on the Gaussian distribution

Cited by 10 publications

References 51 publications

Multiple levels of stochasticity accounted for in different radiation biophysical models: from physics to biology

Multiple levels of stochasticity accounted for in different radiation biophysical models: from physics to biology

On the Emergence of the Deviation from a Poisson Law in Stochastic Mathematical Models for Radiation-Induced DNA Damage: A System Size Expansion

The Determinant of DNA Repair Pathway Choices in Ionising Radiation-Induced DNA Double-Strand Breaks

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