Mechanistic Modelling of Radiation Responses

McMahon, S. J.; Prise, Kevin M.

doi:10.3390/cancers11020205

Cited by 57 publications

(43 citation statements)

References 165 publications

(181 reference statements)

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“…Different theories and models are available to describe this phenomenon, starting from phenomenological to mechanistic ones. We refer interested readers to [ 136 ]. In-vitro, DNA damage can be analyzed by using different methods.…”

Section: Analyzing Resultsmentioning

confidence: 99%

Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective

Possenti

Mecchi

Rossoni

et al. 2021

Cancers

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Ionizing radiation (IR) is used in radiotherapy as a treatment to destroy cancer. Such treatment also affects other tissues, resulting in the so-called normal tissue complications. Endothelial cells (ECs) composing the microvasculature have essential roles in the microenvironment’s homeostasis (ME). Thus, detrimental effects induced by irradiation on ECs can influence both the tumor and healthy tissue. In-vitro models can be advantageous to study these phenomena. In this systematic review, we analyzed in-vitro models of ECs subjected to IR. We highlighted the critical issues involved in the production, irradiation, and analysis of such radiobiological in-vitro models to study microvascular endothelial cells damage. For each step, we analyzed common methodologies and critical points required to obtain a reliable model. We identified the generation of a 3D environment for model production and the inclusion of heterogeneous cell populations for a reliable ME recapitulation. Additionally, we highlighted how essential information on the irradiation scheme, crucial to correlate better observed in vitro effects to the clinical scenario, are often neglected in the analyzed studies, limiting the translation of achieved results.

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Section: Analyzing Resultsmentioning

confidence: 99%

Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective

Possenti

Mecchi

Rossoni

et al. 2021

Cancers

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“…Because the ionization products (radiogenic DNA lesions) produced by low and high LET radiation in DNA show similar chemical complexity and differ mainly in lesion density, we can describe these products in the same terms, namely, isolated single-strand damage, non-DSB clustered lesions, and DSB clustered lesions. As ionization density (LET) increases, it is reasonable to assume that at a particular dose, the number of clustered lesions will increase, a point supported by track structure modeling [41,43,44,47,59,61,80,81]. Of particular importance are clustered DSBs.…”

Section: Biological Effects Of Clustered Dna Lesionsmentioning

confidence: 99%

Clustered DNA Double-Strand Breaks: Biological Effects and Relevance to Cancer Radiotherapy

Nickoloff

Sharma

Taylor

2020

Genes

140

108

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Cells manage to survive, thrive, and divide with high accuracy despite the constant threat of DNA damage. Cells have evolved with several systems that efficiently repair spontaneous, isolated DNA lesions with a high degree of accuracy. Ionizing radiation and a few radiomimetic chemicals can produce clustered DNA damage comprising complex arrangements of single-strand damage and DNA double-strand breaks (DSBs). There is substantial evidence that clustered DNA damage is more mutagenic and cytotoxic than isolated damage. Radiation-induced clustered DNA damage has proven difficult to study because the spectrum of induced lesions is very complex, and lesions are randomly distributed throughout the genome. Nonetheless, it is fairly well-established that radiation-induced clustered DNA damage, including non-DSB and DSB clustered lesions, are poorly repaired or fail to repair, accounting for the greater mutagenic and cytotoxic effects of clustered lesions compared to isolated lesions. High linear energy transfer (LET) charged particle radiation is more cytotoxic per unit dose than low LET radiation because high LET radiation produces more clustered DNA damage. Studies with I-SceI nuclease demonstrate that nuclease-induced DSB clusters are also cytotoxic, indicating that this cytotoxicity is independent of radiogenic lesions, including single-strand lesions and chemically “dirty” DSB ends. The poor repair of clustered DSBs at least in part reflects inhibition of canonical NHEJ by short DNA fragments. This shifts repair toward HR and perhaps alternative NHEJ, and can result in chromothripsis-mediated genome instability or cell death. These principals are important for cancer treatment by low and high LET radiation.

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“…Theoretical approaches valuably complement experimental research on the induction of DNA damage by diverse radiation types under various conditions. In particular, models and simulations help merge information gained from diverse experiments, test putative hypotheses on the action mechanisms, and reveal quantitative characteristics of the underpinning processes 2,3 .…”

Section: Track Structure Based Simulations Valuably Complement Experimentioning

confidence: 99%

“…2 Department of Radiation Dosimetry, Nuclear Physics Institute CAS, Prague, Czech Republic. 3 Radiation Biophysics and Radiobiology Group, Physics Department, University of Pavia, Pavia, Italy. * email: giorgio.baiocco@unipv.it irradiation setup.…”

Section: Track Structure Based Simulations Valuably Complement Experimentioning

confidence: 99%

Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

Kundrát

Friedland

Becker

et al. 2020

Sci Rep

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Track structure based simulations valuably complement experimental research on biological effects of ionizing radiation. They provide information at the highest level of detail on initial DNA damage induced by diverse types of radiation. Simulations with the biophysical Monte Carlo code PARTRAC have been used for testing working hypotheses on radiation action mechanisms, for benchmarking other damage codes and as input for modelling subsequent biological processes. To facilitate such applications and in particular to enable extending the simulations to mixed radiation field conditions, we present analytical formulas that capture PARTRAC simulation results on DNA single- and double-strand breaks and their clusters induced in cells irradiated by ions ranging from hydrogen to neon at energies from 0.5 GeV/u down to their stopping. These functions offer a means by which radiation transport codes at the macroscopic scale could easily be extended to predict biological effects, exploiting a large database of results from micro-/nanoscale simulations, without having to deal with the coupling of spatial scales and running full track-structure calculations.

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Mechanistic Modelling of Radiation Responses

Cited by 57 publications

References 165 publications

Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective

Radiobiological Studies of Microvascular Damage through In Vitro Models: A Methodological Perspective

Clustered DNA Double-Strand Breaks: Biological Effects and Relevance to Cancer Radiotherapy

Analytical formulas representing track-structure simulations on DNA damage induced by protons and light ions at radiotherapy-relevant energies

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