Bystander effects in tumor-free and tumor-bearing rat brains following irradiation by synchrotron X-rays

Fernández-Palomo, Cristian; Schültke, Elisabeth; Smith, Richard; Bräuer-Krisch, Elke; Laissue, Jean A.; Schroll, Christian; Fazzari, Jennifer; Seymour, Colin; Mothersill, Carmel

doi:10.3109/09553002.2013.766770

Cited by 41 publications

(27 citation statements)

References 35 publications

(32 reference statements)

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“…The study by Asur et al 2012 [31] using GRID therapy in mammary carcinoma (SCK) and head and neck cancer (SCCVII) cells showed identical cell survival fraction between medium transfer bystander and direct bystander effect between cells. While Fernandez-Palomo (2013) [32] using synchrotron MRT with doses up to 350 Gy on tumour bearing-mice showed bystander effects in non-irradiated tumour sites. These results showed bystander effects cause cell death to the abscopal area and might explain greater cell killing rate in our study compared to the calculated dose using Monte Carlo simulation.…”

Section: Discussionmentioning

confidence: 99%

An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

et al. 2014

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BackgroundHigh-dose synchrotron microbeam radiation therapy (MRT) has shown the potential to deliver improved outcomes over conventional broadbeam (BB) radiation therapy. To implement synchrotron MRT clinically for cancer treatment, it is necessary to undertake dose equivalence studies to identify MRT doses that give similar outcomes to BB treatments.AimTo develop an in vitro approach to determine biological dose equivalence between MRT and BB using two different cell-based assays.MethodsThe acute response of tumour and normal cell lines (EMT6.5, 4T1.2, NMuMG, EMT6.5ch, 4T1ch5, SaOS-2) to MRT (50–560 Gy) and BB (1.5–10 Gy) irradiation was investigated using clonogenic and real time cell impedance sensing (RT-CIS)/xCELLigence assays. MRT was performed using a lattice of 25 or 50 µm-wide planar, polychromatic kilovoltage X-ray microbeams with 200 µm peak separation. BB irradiations were performed using a Co60 teletherapy unit or a synchrotron radiation source. BB doses that would generate biological responses similar to MRT were calculated by data interpolation and verified by clonogenic and RT-CIS assays.ResultsFor a given cell line, MRT equivalent BB doses identified by RT-CIS/xCELLigence were similar to those identified by clonogenic assays. Dose equivalence between MRT and BB were verified in vitro in two cell lines; EMT6.5ch and SaOS-2 by clonogenic assays and RT-CIS/xCELLigence. We found for example, that BB doses of 3.4±0.1 Gy and 4.40±0.04 Gy were radiobiologically equivalent to a peak, microbeam dose of 112 Gy using clonogenic and RT-CIS assays respectively on EMT6.5ch cells.ConclusionOur data provides the first determination of biological dose equivalence between BB and MRT modalities for different cell lines and identifies RT-CIS/xCELLigence assays as a suitable substitute for clonogenic assays. These results will be useful for the safe selection of MRT doses for future veterinary and clinical trials.

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Section: Discussionmentioning

confidence: 99%

An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

et al. 2014

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“…In particular, angiogenesis could have been promoted to replace damaged capillary blood vessels, whereas the proliferation, migration and differentiation of progenitor glial cells were promoted to produce new, mature and functional glial cells [154]. Recently, through bystander clonogenic reporter assays, Fernandez-Palomo et al [155] demonstrated the presence of the RIBE in healthy and tumor-bearing Wistar rats, which had been exposed to a high dose of radiation (17.5, 35, 70 or 350 Gy) from synchrotron microbeam radiation therapy (MRT) and homogenous synchrotron radiation (HSR). The production of bystander signals was found to be higher in tumorbearing tissues than in tumor-free tissues, which suggested that tumor and normal tissues might induce the RIBE through different mechanisms.…”

Section: In Vivo Studies On Ribe Using Animal Modelsmentioning

confidence: 99%

“…Whereas studies have provided valuable information on the RIBE within tumors, as well as on abscopal effects on tumors [3,[153][154][155], we might be able to gain extra insight into non-targeted effects by studying radiobiological effects of ionizing radiation on tumors through developing an embryo model. The embryonic origin of tumors has been gaining ground in the past few decades (e.g., see review by Ma et al [188]), and attempts have begun to fight cancer from the perspective of developmental biology [189,190].…”

Section: Embryogenesis and Tumorigenesismentioning

confidence: 99%

Embryos of the zebrafish Danio rerio in studies of non-targeted effects of ionizing radiation

Choi

2015

Cancer Letters

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“…So far, the experimental data of radiation-induced abscopal effect almost all come from in vivo studies [26–28]. Many in vitro studies have been performed to investigate the intrinsic of radiation induced bystander effect (RIBE) by co-culturing irradiated tumor cells with nonirradiated normal cells [29–31].…”

Section: Introductionmentioning

confidence: 99%

The differential role of human macrophage in triggering secondary bystander effects after either gamma-ray or carbon beam irradiation

Dong

et al. 2015

Cancer Letters

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The abscopal effect could be an underlying factor in evaluating prognosis of radiotherapy. This study established an in vitro system to examine whether tumor-generated bystander signals could be transmitted by macrophages to further trigger secondary cellular responses after different irradiations, where human lung cancer NCI-H446 cells were irradiated with either γ-rays or carbon ions and co-cultured with human macrophage U937 cells, then these U937 cells were used as a bystander signal transmitter and co-cultured with human bronchial epithelial cells BEAS-2B. Results showed that U937 cells were only activated by γ-irradiated NCI-H446 cells so that the secondary injuries in BEAS-2B cells under carbon ion irradiation were weaker than γ-rays. Both TNF-α and IL-1α were involved in γ-irradiation induced secondary bystander effect but only TNF-α contributed to the carbon ion induced response. Further assay disclosed that IL-1α but not TNF-α was largely responsible for the activation of macrophages and the formation of micronucleus in BEAS-2B cells. These data suggest that macrophages could transfer secondary bystander signals and play a key role in the secondary bystander effect of photon irradiation while carbon ion irradiation has conspicuous advantage due to its reduced secondary injury.

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Bystander effects in tumor-free and tumor-bearing rat brains following irradiation by synchrotron X-rays

Abstract: The RIBE observed in our reporter cells shows that both MRT and HSR yield a demonstrable abscopal effect after high doses of irradiation; presumably as part of a systemic response.

Cited by 41 publications

References 35 publications

An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

An Evaluation of Dose Equivalence between Synchrotron Microbeam Radiation Therapy and Conventional Broadbeam Radiation Using Clonogenic and Cell Impedance Assays

Embryos of the zebrafish Danio rerio in studies of non-targeted effects of ionizing radiation

The differential role of human macrophage in triggering secondary bystander effects after either gamma-ray or carbon beam irradiation

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