Temporally distinct response of irradiated normal human fibroblasts and their bystander cells to energetic heavy ions

Hamada, Nobuyuki; Ni, Meinan; Funayama, Tomoo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

doi:10.1016/j.mrfmmm.2007.11.001

Cited by 54 publications

(25 citation statements)

References 53 publications

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“…Several investigators have elucidated this phenomenon in detail using the microbeam irradiation system, which can individually deliver a precise number of charged particles to the cells, as Nagasawa and Little first reported the cell-killing effect from irradiated cells to non-irradiated cells. (3,10,25) Sawant et al reported that a 1-40% reduction in the surviving fraction was observed in non-irradiated cells when 10% of the nuclei of the cultured cells were actually traversed by 1-16 α-particles per cell in Chinese hamster V79 cells. (29) In our study, the heavy-ion microbeam apparatus was used to investigate the impact of the bystander effect on cell killing in a clonogenic assay.…”

Section: Discussionmentioning

confidence: 99%

“…(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%

“…(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. Likewise, in sparse cultures, 7.4 × 10 4 ± 2.9 × 10 4 cells/dish were populated, and the fraction of hit cells was estimated to be 0.001, 0.007, and 0.03% when 1, 5, and 25 cells were targeted.…”

Section: Methodsmentioning

confidence: 99%

“…(25)(26)(27) The LET at the cell surface was calculated according to the kinetic energy loss, assuming water equivalence. Dose (Gy) was calculated as fluence (ion particles/ cm 2 ) × LET (keV/μm) × 1.6 × 10 -9 .…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

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: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Harada¹,

Nonaka²,

Hamada

et al. 2009

Cancer Science

Self Cite

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“…Cell survival was determined using the clonogenic survival assay as described elsewhere (Hamada et al, 2006(Hamada et al, , 2008c(Hamada et al, , 2008d. Briefly, confluent cultures were reinoculated within 1 h postirradiation into 100-mm tissue culture dishes (3020-100, Iwaki) in quadruplicate, and were incubated for 12-13 days, at which time they were fixed in methanol and stained with crystal violet.…”

Section: Cell Survival Analysismentioning

confidence: 99%

A LET-Dependent Decrease in the Apoptotic Response of Normal Human Fibroblast Cultures to Isosurvival Doses of γ-Rays and Energetic Heavy Ions

Hamada

Funayama

et al. 2008

Biol. Sci. Space

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Biological effectiveness varies with the linear energy transfer (LET) of ionizing radiation. Plentiful evidence has been presented demonstrating that at physically equivalent doses, high-LET energetic heavy ions are more cytotoxic and genotoxic than low-LET photons like X-rays and γ-rays. Notwithstanding, its potential impact at isosurvival doses is yet to be characterized. Here we investigated the cell-killing effectiveness of γ-rays (0.2 keV/µm) and five different beams of heavy ions with LET ranging from 16.2 to 1610 keV/µm in confluent cultures of normal human fibroblasts. The relative biological effectiveness based on the dose giving 10% clonogenic survival peaked at 108 keV/µm. In cultures exposed to the 10% survival doses, the yield of apoptotic cells escalated with time postirradiation but declined with LET. Our results imply that the cell death mode differs with LET at isosurvival levels.

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The Radiobiology of Particle Therapy

Fossati¹,

Tubin²,

Hug³

2022

Principles and Practice of Particle Therapy

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Temporally distinct response of irradiated normal human fibroblasts and their bystander cells to energetic heavy ions

Cited by 54 publications

References 53 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

A LET-Dependent Decrease in the Apoptotic Response of Normal Human Fibroblast Cultures to Isosurvival Doses of γ-Rays and Energetic Heavy Ions

The Radiobiology of Particle Therapy

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