Systemic mechanisms and effects of ionizing radiation: A new ⿿old⿿ paradigm of how the bystanders and distant can become the players

Nikitaki, Zacharenia; Mavragani, Ifigeneia V.; Laskaratou, Danae A.; Gika, V.; Moskvin, V.; Theofilatos, Konstantinos; Vougas, Konstantinos; Stewart, Robert D.; Georgakilas, Alexandros G.

doi:10.1016/j.semcancer.2016.02.002

Cited by 104 publications

(88 citation statements)

References 124 publications

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“…This could be due to the direct exposure of blood which was passing through the exposure area at the time of radiation and possibly due to bystander effect. Similar observations have been previously proved under in vitro and ex vivo conditions [39][40][41][42] . Considering all the results, our study indicates that the normal cells get adapted to damage due to multiple low dose exposure.…”

Section: Discussionsupporting

confidence: 89%

Response of Normal Cells Following Multiple Radiation Exposure under Radiotherapy Setting

et al. 2017

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Radiotherapy is an established approach for killing of tumour cells. During the process, most of the normal cells also get affected due to direct exposure or by bystander effects. To measure the damage pattern in healthy cells, a pilot study was designed under radiotherapy settings. Right leg region of Strain ‘A’ male mice was locally exposed to Cobalt60 gamma radiation with a dose of 2 Gy/ day for 5 consecutive days. After completion of each fraction, blood haematology and γH2AX studies were performed at 1 h time point in blood and bone marrow cells. Chromosomal aberration study in bone marrow was carried out at 24 h post irradiation of each fraction for evaluation of DNA damage. γH2AX and chromosomal aberration were found significantly (p<0.001) increased with each consecutive dose upto 4th fractions. Blood hematology showed a linear reduction in total WBC counts which included the reduction in lymphocytes and increased granulocytes with each passing dose up to 4th fraction. However, non significant damage (p>0.05) for all parameters have been observed for 4th and 5th split doses. The study indicated that repeated exposure leads to damage fixation in normal cells, possibly indicating a state of adaptation.

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Section: Discussionsupporting

confidence: 89%

Response of Normal Cells Following Multiple Radiation Exposure under Radiotherapy Setting

et al. 2017

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“…In parallel, we further explored the validity of one of the aforementioned derived DE gene lists, particularly the one formed from the union of bystander comparisons from the GSE18760, GSE12435 and GSE8993 datasets, with a reference literature-mined gene list regarding RIBE, proposed by the study of Nikitaki et.al [45]. From this comparison, 22 from the 74 genes were identified as common, including mostly interleukins, chemokines and genes associated with apoptosis ( Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE) 

Yeles

Vlachavas

Papadodima

et al. 2017

Preprint

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Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, negative regulation of growth, cellular response to Zn2+-Cd2+, Wnt and NIK/NFkappaB signalling, which refine the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations like α-particles and carbon-ions.

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“…In a close collaboration with Iliakis' (Germany), Ravanat's (France), and Martin's (Australia) groups, the DNA Damage Laboratory of A. Georgakilas (NTUA, Greece) has proposed an improvement of methodologies used for the detection of oxidative clustered DNA lesions in vitro and in vivo with special emphasis on the in situ detection including bystander effects [62][63][64][65]. In addition, bioinformatics has been used to better understand the DNA damage response mechanisms relating to ionizing radiationinduced DNA damage and their association with inflammatory and immune response pathways [66][67][68][69][70][71]. Collaboration between the groups of Monari and Dumont (France), and the Georgakilas group, through the application of Molecular Dynamics (MD) simulations, gave mechanistic insights on the processing of clustered DNA lesions especially for cases where it is very difficult to acquire analytical experimental data [72,73].…”

Section: Working Group 2: Models Of Dna Damage and Consequencesmentioning

confidence: 99%

“…There are a few exceptions that have been examined in these papers. In addition, through the use of Monte Carlo (MD) simulations, a special biophysical model was developed for the simulation of radiation-induced systemic effects and the interpretation of various nontargeted effects [67]. Last but not least, in a series of publications, Georgakilas' group within its participation in the network of the Halifax Project contributed toward the designing of a broad-spectrum integrative approach for cancer prevention and treatment as reviewed in [73,74].…”

Section: Working Group 2: Models Of Dna Damage and Consequencesmentioning

confidence: 99%

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

Ferreri

Golding

Jahn

et al. 2016

Free Radical Research

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The COST Action CM1201 "Biomimetic Radical Chemistry" has been active since December 2012 for 4 years, developing research topics organized into four working groups: WG1 -Radical Enzymes, WG2 -Models of DNA damage and consequences, WG3 -Membrane stress, signalling and defenses, and WG4 -Bio-inspired synthetic strategies. International collaborations have been established among the participating 80 research groups with brilliant interdisciplinary achievements. Free radical research with a biomimetic approach has been realized in the COST Action and are summarized in this overview by the four WG leaders. ARTICLE HISTORY

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Systemic mechanisms and effects of ionizing radiation: A new ⿿old⿿ paradigm of how the bystanders and distant can become the players

Cited by 104 publications

References 124 publications

Response of Normal Cells Following Multiple Radiation Exposure under Radiotherapy Setting

Response of Normal Cells Following Multiple Radiation Exposure under Radiotherapy Setting

Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

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Systemic mechanisms and effects of ionizing radiation: A new ⿿old⿿ paradigm of how the bystanders and distant can become the players

Cited by 104 publications

References 124 publications

Response of Normal Cells Following Multiple Radiation Exposure under Radiotherapy Setting

Response of Normal Cells Following Multiple Radiation Exposure under Radiotherapy Setting

Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)&nbsp;

COST Action CM1201 “Biomimetic Radical Chemistry”: free radical chemistry successfully meets many disciplines

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Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)