Expression profiles are different in carbon ion-irradiated normal human fibroblasts and their bystander cells

Iwakawa, Mayumi; Hamada, Nobuyuki; Imadome, Kaori; Funayama, Tomoo; Sakashita, Testuya; Kobayashi, Yasuhiko; Imai, Takashi

doi:10.1016/j.mrfmmm.2008.04.007

Cited by 48 publications

(40 citation statements)

References 47 publications

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“…(20) Targeted heavy-ion irradiation to only a very small fraction of cells within the whole cell population was carried out using microbeams installed at the Takasaki Ion Accelerator for Advanced Radiation Application of Japan Atomic Energy Agency, for which the set-up and irradiation procedures have been described. (10,18,(21)(22)(23)(24)(25) By using microbeams collimated through a 20-μm-diameter aperture, each of 1, 5, or 25 cells within the whole population was targeted with the precise number of carbon ions (18.3 MeV/u, LET = 103 keV/μm), as described previously. (10,18,25) In a dish, 1.3 × 10 6 ± 0.4 × 10 6 cells were populated in confluent cultures that were then irradiated, and then the fraction of hit cells among the whole population was estimated to be 0.0001, 0.0004, and 0.002% when 1, 5, and 25 cells were targeted.…”

Section: Methodsmentioning

confidence: 99%

Heavy‐ion‐induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication

Harada¹,

Nonaka²,

Hamada

et al. 2009

Cancer Science

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It is thought that heavy-ion radiation therapy is a promising modality of cancer therapy that can deliver higher biological effects on tumors than conventional X-ray radiation therapy, and may also conserve the function of normal organs because of its excellent dose distribution.(1) Recently, excellent clinical results were reported in the treatment of lung cancer, prostate cancer, cancer of the head and neck, and malignant tumors of bone and soft tissue.(2) Heavy-ion has high linear energy transfer (LET) with increased relative biological effectiveness (RBE). However, the possible mechanism of increasing cell killing in heavyion therapy is not fully understood. Previous studies have demonstrated that the induction of cell killing of non-irradiated cells by adjacent cells that are directly irradiated by heavy-ions is considered to play an important role in radiation-induced cell death, not only in tumors but also in normal organs. This phenomenon is termed the "bystander effect", and was reported by Nagasawa and Little in 1992.(3) They reported that increased sister chromatid exchanges were observed in more than 30% of cells when less than 1% of the nuclei of cultured cells were actually traversed by an α-particle in Chinese hamster ovary cells. It has been proposed that the mediating mechanism involves secreted soluble factors, (4)(5)(6) an increase in oxidative stress,plasma membrane-bound lipid rafts, (8) and gap junctional intracellular communication (GJIC). (4,7,(9)(10)(11)(12)(13) Gap junctions are membrane channels that connect the cytoplasm of cells and allow direct exchange of small molecules and ions between adjacent cells. GJIC is essential for the maintenance of tissue homeostasis and proliferation and the regulation of embryonic development and differentiation, and it plays a key role in induction of the bystander effect. (14)(15)(16)(17) Here, bystander killing of cells by heavy-ion irradiation was investigated, focusing on the involvement of GJIC on cell survival, to clarify the underlying mechanisms of the bystander effect in a human lung cancer cell line in vitro. Materials and MethodsCell cultures. A549 (a human lung cancer cell line with wild-type p53) was obtained from the Cell Resource Center for Biomedical Research at the Institute of Development, Aging and Cancer, Tohoku University, Japan. Cells were cultured in RPMI-1640 medium (Immuno-Biological Laboratories, Takasaki, Japan) supplemented with 10% fetal calf serum (PAA Laboratories, Pasching, Austria). Two days prior to irradiation experiments, 5 × 10 5 and 5 × 10 4 cells were inoculated into a specially designed 35-mm microbeam dish that was constructed as previously described, (18) to prepare confluent cultures and sparsely populated cultures, respectively. Unless otherwise described, all cell cultures were maintained at 37°C in a humidified atmosphere of 5% CO 2 in air. The size of the cell nucleus and the whole cells was determined to be 14.6 ± 4.3 and 106 ± 24.9 μm 2 , respectively. Drug treatment. Prior to irradiation, cells were p...

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Section: Methodsmentioning

confidence: 99%

Heavy‐ion‐induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication

Harada¹,

Nonaka²,

Hamada

et al. 2009

Cancer Science

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“…In the current study, the application of an integrative workflow to seven RIBE-related microarray datasets deposited in GEO (GSE55869 [32] , GSE32091 [33], GSE21059 [34], GSE25772 [35], GSE18760 [36], GSE12435 [37], GSE8993 [38]), led to interesting findings regarding the underlying molecular mechanisms.…”

Section: Discussionmentioning

confidence: 87%

“…Specific microarray datasets were selected from the public repository GEO, using the term "radiation bystander effect". From the total 10 results with human cell lines, seven microarray datasets related to RIBE (GSE55869 [32] , GSE32091 [33], GSE21059 [34], GSE25772 [35], GSE18760 [36], GSE12435 [37], GSE8993 [38]) have been used for the analysis. The remaining three datasets have been excluded for reasons of inconsistency between files of sample and data relationship format and different purpose of the experiment.…”

Section: Data Acquisitionmentioning

confidence: 99%

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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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“…AG01522D primary normal human foreskin diploid fibroblasts were purchased and maintained as previously described (Hamada et al, 2006;Iwakawa et al, 2008). Cells at passage 9 were seeded at 200 cells/cm 2 on 6-cm dishes, and incubated at 37˚C in a humidified atmosphere of 5% CO 2 in air, at which time irradiation was carried out at room temperature as mentioned (Hamada et al, 2008b(Hamada et al, , 2008c(Hamada et al, , 2008d.…”

Section: Cell Culture and Irradiationmentioning

confidence: 99%

Exposure of Normal Human Fibroblasts to Heavy-Ion Radiation Promotes Their Morphological Differentiation

et al. 2008

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Here we investigated the potential impact of energetic heavy ions on fibroblast differentiation. The differentiation pattern was morphologically determined at days 3 and 5 after exposure to graded dose of γ-rays (0.2 keV/µm) or carbon ions (18.3 MeV/u, 108 keV/µm). The cells irradiated with higher doses progressed toward later differentiation stages as time goes postirradiation, but underwent fewer cell divisions. Thus, radiation exposure accelerated morphological differentiation, for which carbon ions were more effective than γ-rays. The relative biological effectiveness of carbon ions for differentiation was higher than that for the clonogenic survival, and this was the most case for terminally differentiated cells that may not divide any more. The results are suggestive of the distinct mechanism underlying inactivation of clonogenic potential between the radiation quality, such that the contribution of the differentiation to heavy ion-induced reductions in the survival is greater than to those induced by photons. Such accelerated differentiation could be a protective mechanism that minimizes further expansion of aberrant cells.

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Expression profiles are different in carbon ion-irradiated normal human fibroblasts and their bystander cells

Cited by 48 publications

References 47 publications

Heavy‐ion‐induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication

Heavy‐ion‐induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication

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

Exposure of Normal Human Fibroblasts to Heavy-Ion Radiation Promotes Their Morphological Differentiation

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Expression profiles are different in carbon ion-irradiated normal human fibroblasts and their bystander cells

Cited by 48 publications

References 47 publications

Heavy‐ion‐induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication

Heavy‐ion‐induced bystander killing of human lung cancer cells: Role of gap junctional intercellular communication

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

Exposure of Normal Human Fibroblasts to Heavy-Ion Radiation Promotes Their Morphological Differentiation

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