Datasets of in vitro clonogenic assays showing low dose hyper-radiosensitivity and induced radioresistance

Polgár, Szabolcs; Schofield, Paul N.; Madas, Balázs G.

doi:10.1038/s41597-022-01653-3

Cited by 2 publications

(2 citation statements)

References 75 publications

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“…Large scale research programs (see, for example, the USA DOE program 1999 [65], http://lowdose.energy.gov, 6 December 2012 accessed 30 June 2023) as well as the more focused European program coordinated by MELODI (1999) on low doses < 100 mGy were launched in order to obtain a better scientific understanding of low-dose radiation responses [62]. Important classical and recent low-dose radiation phenomena were brought to light and investigated in depth, notably hormesis [66][67][68][69], radioadaptation [70], hyper-radiation sensitivity (HRS) [70,71], bystander effects and non-targeted effects [1,5,70,72], and genomic instability [5,70]. Importantly, these effects were found to be The present paper focuses on low-dose radiation effects and non-targeted effects (NTE) involving mitochondrial functions.…”

Section: Low-dose Radiation Effectsmentioning

confidence: 99%

“…Low-dose hyper-radiosensitivity (HRS) is a typical low-dose IR phenomenon (see, for review, [19,69]), and it is evidenced by many datasets [71]. It was first reported by Joiner et al [153], and it is characterized by an early dip in the survival curves of mammalian cells, indicating hypersensitivity to IR at doses between 100-300 mGy followed by radioresistance (IRR) at higher doses [153][154][155].…”

Section: Low Dose Hyper-radiation Sensitivity (Hrs) and Induction Of ...mentioning

confidence: 99%

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Low-Dose Non-Targeted Effects and Mitochondrial Control

Averbeck

2023

IJMS

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Non-targeted effects (NTE) have been generally regarded as a low-dose ionizing radiation (IR) phenomenon. Recently, regarding long distant abscopal effects have also been observed at high doses of IR) relevant to antitumor radiation therapy. IR is inducing NTE involving intracellular and extracellular signaling, which may lead to short-ranging bystander effects and distant long-ranging extracellular signaling abscopal effects. Internal and “spontaneous” cellular stress is mostly due to metabolic oxidative stress involving mitochondrial energy production (ATP) through oxidative phosphorylation and/or anaerobic pathways accompanied by the leakage of O2− and other radicals from mitochondria during normal or increased cellular energy requirements or to mitochondrial dysfunction. Among external stressors, ionizing radiation (IR) has been shown to very rapidly perturb mitochondrial functions, leading to increased energy supply demands and to ROS/NOS production. Depending on the dose, this affects all types of cell constituents, including DNA, RNA, amino acids, proteins, and membranes, perturbing normal inner cell organization and function, and forcing cells to reorganize the intracellular metabolism and the network of organelles. The reorganization implies intracellular cytoplasmic-nuclear shuttling of important proteins, activation of autophagy, and mitophagy, as well as induction of cell cycle arrest, DNA repair, apoptosis, and senescence. It also includes reprogramming of mitochondrial metabolism as well as genetic and epigenetic control of the expression of genes and proteins in order to ensure cell and tissue survival. At low doses of IR, directly irradiated cells may already exert non-targeted effects (NTE) involving the release of molecular mediators, such as radicals, cytokines, DNA fragments, small RNAs, and proteins (sometimes in the form of extracellular vehicles or exosomes), which can induce damage of unirradiated neighboring bystander or distant (abscopal) cells as well as immune responses. Such non-targeted effects (NTE) are contributing to low-dose phenomena, such as hormesis, adaptive responses, low-dose hypersensitivity, and genomic instability, and they are also promoting suppression and/or activation of immune cells. All of these are parts of the main defense systems of cells and tissues, including IR-induced innate and adaptive immune responses. The present review is focused on the prominent role of mitochondria in these processes, which are determinants of cell survival and anti-tumor RT.

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Section: Low-dose Radiation Effectsmentioning

confidence: 99%

Section: Low Dose Hyper-radiation Sensitivity (Hrs) and Induction Of ...mentioning

confidence: 99%

Low-Dose Non-Targeted Effects and Mitochondrial Control

Averbeck

2023

IJMS

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Method for Determining Radioresistance of Cancer Cell Lines Based on Cluster Analysis of Clonogenic Cell Survival Data

Wannouss,

Semel,

Golyshev

et al. 2024

Med. fiz.

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Background: The outcome of radiation therapy, the duration and quality of life of cancer patients significantly depend on the radiosensitivity (RS) of a cancerous tumor, and the duration of the patient’s relapse-free period is largely determined by the degree of its radioresistance (RR). Today the results of molecular mechanism investigation of cancer radioresistance and the classification of cancer cells according to their radiophenotypes mostly contribute to improving prognosis methods of treatment outcomes and increasing effectiveness of radiation therapy. In this work, we developed a classification method of cancer cells according to their radiosensitivity using machine learning based on the data analysis of clonogenic cell survival under ionizing radiation. Material and methods: The method consists of clustering parameters of experimental dose-effect relationships, which were approximated using the equation of a linear-quadratic (LQ) model, which is used to evaluate RS of cancer cells in radiobiology. The training of the statistical model included published experimental dataset of 96 cancer cell lines, for which parameters a, b and their ratio a/b of the LQ model were determined. Classification of cancer cells according to their radiosensitivity was carried out based on principal component analysis (PCA) in the parameter space (a, a/b), k-means clustering and hierarchical clustering methods. Results: Application of the developed statistical model to a large dataset of cancer cells made it possible to reliably separate radiosensitive and radioresistant (RR) cells into two clusters according to the parameters a and a/b. Application of the model to cancer cells with acquired RR, in which RS was suppressed as a result of exposure to irradiation or hypoxia, allowed tracing the shift of parent cells’ parameters from the RS cluster to the RR cell cluster. To study the genetic mechanisms of radiosensitivity, we performed bioinformatic analysis of the mutation distribution in genes encoding proteins in the cellular signalling pathways of cancer cells, i.e. proliferation, apoptosis, repair of damaged DNA molecules and antioxidant defence cellular system. Conclusion: The developed statistical model of radiophenotypic classification of cancer cells based on their radiosensitivity can be used in the development of radiation therapy treatment plans taking into account radiosensitivity of patient’s tumour. The model may be also helpful in a joint analysis of the phenotypic and genotypic characteristics of cancer cells, aiming at the elucidation of the molecular and genetic mechanisms of radiosensitivity and development of biomarkers of radioresistance.

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Datasets of in vitro clonogenic assays showing low dose hyper-radiosensitivity and induced radioresistance

Cited by 2 publications

References 75 publications

Low-Dose Non-Targeted Effects and Mitochondrial Control

Low-Dose Non-Targeted Effects and Mitochondrial Control

Method for Determining Radioresistance of Cancer Cell Lines Based on Cluster Analysis of Clonogenic Cell Survival Data

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