Comparison of X-ray and alpha particle effects on a human cancer and endothelial cells: Survival curves and gene expression profiles

Riquier, Hélène; Wéra, Anne-Catherine; Heuskin, Anne-Catherine; Feron, Olivier; Lucas, Stéphane; Michiels, Carine

doi:10.1016/j.radonc.2013.02.017

Cited by 22 publications

(26 citation statements)

References 23 publications

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“…For example, using human peripheral blood mononuclear cells, Chauhan et al [10] found that the gene expression profile induced by α-particle radiation was very similar to the x-ray responses, despite the fact that α-particles are characterized by a higher linear energy transfer coefficient compared with x-rays [11]. In contrast, comparison of α-particle and x-ray irradiation impact on human tumor and endothelial cells [12], as well as human epidermal keratinocytes [13] produced distinct gene expression profiles.…”

Section: Introductionmentioning

confidence: 99%

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Broustas

Harken

et al. 2017

BMC Genomics

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BackgroundIn the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of photons plus a neutron component that would contribute to the total dose. As neutrons cause more complex and difficult to repair damage to cells that would result in a more severe health burden to affected individuals, it is paramount to be able to estimate the contribution of neutrons to an estimated dose, to provide information for those making treatment decisions.ResultsMice exposed to either 0.25 or 1 Gy of neutron or 1 or 4 Gy x-ray radiation were sacrificed at 1 or 7 days after exposure. Whole genome microarray analysis identified 7285 and 5045 differentially expressed genes in the blood of mice exposed to neutron or x-ray radiation, respectively. Neutron exposure resulted in mostly downregulated genes, whereas x-rays showed both down- and up-regulated genes. A total of 34 differentially expressed genes were regulated in response to all ≥1 Gy exposures at both times. Of these, 25 genes were consistently downregulated at days 1 and 7, whereas 9 genes, including the transcription factor E2f2, showed bi-directional regulation; being downregulated at day 1, while upregulated at day 7. Gene ontology analysis revealed that genes involved in nucleic acid metabolism processes were persistently downregulated in neutron irradiated mice, whereas genes involved in lipid metabolism were upregulated in x-ray irradiated animals. Most biological processes significantly enriched at both timepoints were consistently represented by either under- or over-expressed genes. In contrast, cell cycle processes were significant among down-regulated genes at day 1, but among up-regulated genes at day 7 after exposure to either neutron or x-rays. Cell cycle genes downregulated at day 1 were mostly distinct from the cell cycle genes upregulated at day 7. However, five cell cycle genes, Fzr1, Ube2c, Ccna2, Nusap1, and Cdc25b, were both downregulated at day 1 and upregulated at day 7.ConclusionsWe describe, for the first time, the gene expression profile of mouse blood cells following exposure to neutrons. We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3436-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Broustas

Harken

et al. 2017

BMC Genomics

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“…9 Although SRS scoring systems have been developed and validated in clinical practice, 31 understanding the biological response of endothelium to radiation may permit a more accurate prediction of SRS outcomes. Radiation-induced changes in some cells, such as cancer cells, have been investigated; 17,18,34 however, the relevant studies in brain endothelial cells are limited, especially at the molecular level.…”

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confidence: 99%

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

Zhao

Johnson

Chen

et al. 2016

JNS

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Brain arteriovenous malformations (AVMs) are congenital abnormalities that consist of direct connections between arteries and veins, allowing highpressure arterial blood to flow into fragile cerebral veins, resulting in a high risk of hemorrhagic stroke. 16,37 The aim of AVM treatment is to prevent hemorrhage. 29 Treatment is effective only with complete AVM removal or obliteration. 14 Current treatments-namely surgery, endovascular occlusion, or stereotactic radiosurgery-are all associated with significant limitations.1,42 The surgical risk is generally unacceptable for lesions that are large, located in critical brain structures, or involve deep perforating arterabbreviatioNs AVM = arteriovenous malformation; FWD = forward; PI = propidium iodide; PS = phosphatidylserine; pSIVA = polarity-sensitive indicator of viability and apoptosis; SRS = stereotactic radiosurgery. obJective Stereotactic radiosurgery (SRS) is an established intervention for brain arteriovenous malformations (AVMs). The processes of AVM vessel occlusion after SRS are poorly understood. To improve SRS efficacy, it is important to understand the cellular response of blood vessels to radiation. The molecular changes on the surface of AVM endothelial cells after irradiation may also be used for vascular targeting. This study investigates radiation-induced externalization of phosphatidylserine (PS) on endothelial cells using live-cell imaging. methods An immortalized cell line generated from mouse brain endothelium, bEnd.3 cells, was cultured and irradiated at different radiation doses using a linear accelerator. PS externalization in the cells was subsequently visualized using polarity-sensitive indicator of viability and apoptosis (pSIVA)-IANBD, a polarity-sensitive probe. Live-cell imaging was used to monitor PS externalization in real time. The effects of radiation on the cell cycle of bEnd.3 cells were also examined by flow cytometry. results Ionizing radiation effects are dose dependent. Reduction in the cell proliferation rate was observed after exposure to 5 Gy radiation, whereas higher radiation doses (15 Gy and 25 Gy) totally inhibited proliferation. In comparison with cells treated with sham radiation, the irradiated cells showed distinct pseudopodial elongation with little or no spreading of the cell body. The percentages of pSIVA-positive cells were significantly higher (p = 0.04) 24 hours after treatment in the cultures that received 25- and 15-Gy doses of radiation. This effect was sustained until the end of the experiment (3 days). Radiation at 5 Gy did not induce significant PS externalization compared with the sham-radiation controls at any time points (p > 0.15). Flow cytometric analysis data indicate that irradiation induced growth arrest of bEnd.3 cells, with cells accumulating in the G2 phase of the cell cycle. coNclusioNs Ionizing radiation causes remarkable cellular changes in endothelial cells. Significant PS externalization is induced by radiation at doses of 15 Gy or higher, concomitant with a block in the cell cycle. Ra...

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“…We hypothesize that such phenomena are caused by individual cell death in the blood vessel, which compromises the vessel. We therefore anticipate dose dependence and we propose to use classic cell death measured in human endothelial cells 25 as a first approximation for blood vessel disruption. This is implemented in automata by the classic linear quadratic model 26, 27 and Monte Carlo approaches.…”

Section: Methodsmentioning

confidence: 99%

“…In our 2D tumour model, whenever a vessel is exposed to a given dose fraction fracD , we compute the probability of losing one cell as the hit probability, where α ec and β ec have been computed from the experimental data in ref. 25: …”

Section: Methodsmentioning

confidence: 99%

Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes

Paul‐Gilloteaux

Potiron

Delpon

et al. 2017

Sci Rep

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The concept of hypofractionation is gaining momentum in radiation oncology centres, enabled by recent advances in radiotherapy apparatus. The gain of efficacy of this innovative treatment must be defined. We present a computer model based on translational murine data for in silico testing and optimization of various radiotherapy protocols with respect to tumour resistance and the microenvironment heterogeneity. This model combines automata approaches with image processing algorithms to simulate the cellular response of tumours exposed to ionizing radiation, modelling the alteration of oxygen permeabilization in blood vessels against repeated doses, and introducing mitotic catastrophe (as opposed to arbitrary delayed cell-death) as a means of modelling radiation-induced cell death. Published data describing cell death in vitro as well as tumour oxygenation in vivo are used to inform parameters. Our model is validated by comparing simulations to in vivo data obtained from the radiation treatment of mice transplanted with human prostate tumours. We then predict the efficacy of untested hypofractionation protocols, hypothesizing that tumour control can be optimized by adjusting daily radiation dosage as a function of the degree of hypoxia in the tumour environment. Further biological refinement of this tool will permit the rapid development of more sophisticated strategies for radiotherapy.

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Comparison of X-ray and alpha particle effects on a human cancer and endothelial cells: Survival curves and gene expression profiles

Cited by 22 publications

References 23 publications

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Comparison of gene expression response to neutron and x-ray irradiation using mouse blood

Live-cell imaging to detect phosphatidylserine externalization in brain endothelial cells exposed to ionizing radiation: implications for the treatment of brain arteriovenous malformations

Optimizing radiotherapy protocols using computer automata to model tumour cell death as a function of oxygen diffusion processes

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