Heavy-Ion Microbeam System at JAEA-Takasaki for Microbeam Biology

Funayama, Tomoo; Wada, Seiichi; Yokota, Yuichiro; Fukamoto, Kana; Sakashita, Tetsuya; Taguchi, Mitsumasa; Kakizaki, Takehiko; Hamada, Nobuyuki; Suzuki, Michiyo; Furusawa, Yoshiya; Watanabe, Hiroshi; Kiguchi, Kenji; Kobayashi, Yasuhiko

doi:10.1269/jrr.07085

Cited by 62 publications

(33 citation statements)

References 42 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%

“…(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%

“…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.…”

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confidence: 99%

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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%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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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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“…The beam characteristics and dosimetry of carbon ion-microbeam irradiations have been described elsewhere [10,12,19]. The preparation of cell samples have been described in detail previously.…”

Section: Carbon Ion Microbeam Irradiationmentioning

confidence: 99%

A correlation of long term effects and radiation quality in the progeny of bystander cells after microbeam radiations: The experimental study of radiotherapy for cancer risk mitigation

Autsavapromporn

Konishi

Liu

et al. 2017

J. Phys.: Conf. Ser.

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Abstract. The goal of this study is to investigate the role of radiation quality and gap junction intercellular communication (GJIC) in the propagation of delayed stressful effects in the progeny of bystander human skin fibroblasts cultures (NB1RGB). Briefly, confluent NB1RGB cells in the presence and absence of gap junction inhibitor (AGA) were exposed to ionizing radiation (IR) with a different linear energy transfer (LET) either 5.35 keV X rays (LET 6 keV/m) or 18.3 MeV/u carbon (LET 103 keV/m) microbeam radiations. Following 20 populations post-irradiation, the progeny of bystander NB1RGB cells were harvested and assayed for several of biological endpoints. Our results showed that expression of stressful effects in the progeny of bystander cells is dependent on LET. The progeny of bystander cells exposed to low-LET X rays showed the persistence of oxidative stress and it was correlated with the increased mutant fraction. Such effect were not observed after high-LET carbon ions. Interestingly, inhibition of GJIC mitigated the toxic effects in the progeny of bystander cells. Together, the results contribute to the understanding of the fundamental radiation biology relating to the high-LET carbon ions to mitigate cancer risk after radiotherapy. Furthermore, GJIC be considered as a critical mediator in the bystander mutagenic effect.

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“…Targeted microbeam irradiation of cell subpopulations (referred hereafter to as microirradiation) was performed using collimated microbeams installed at TIARA (Takasaki Ion Accelerators for Advanced Radiation Application) facilities of Japan Atomic Energy Agency (JAEA), for which the setup and irradiation procedure have been described (Kobayashi et al, 2004;Funayama et al, 2008aFunayama et al, , 2008b. Paraffin with a melting temperature of 60-62˚C (Wako, Osaka, Japan) was used to glue the 25-mm-diameter and 200-µm-thick Thermanox coversplip (Nalge Nunc, Roychester, NY) onto a 35-mmdiameter polystyrene dish whose bottom has a 12-mmdiameter center hole (Asashi Techno Glass, Chiba, Japan).…”

Section: Heavy-ion Irradiationmentioning

confidence: 99%

Heavy-Ion Microbeam Irradiation Induces Bystander Killing of Human Cells

et al. 2008

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Significant evidence indicates that ionizing radiation causes biological effects in nonirradiated bystander cells having received signals from directly irradiated cells. There is little information available hitherto as to the bystander effect of energetic heavy ions; however, our previous work has shown that in confluent cultures of normal human fibroblast AG01522 cells, targeted exposure of 0.0003% of cells to microbeams of 18.3 MeV/u 12 C (103 keV/µm) and 13.0 MeV/u 20 Ne (375 keV/µm) ions can similarly cause almost 10% decreases in the clonogenic survival, and twofold increments in the incidence of apoptosis whose temporal kinetics varies between irradiated and bystander cells. Using this experimental system, here we further report that bystander responses of AG01522 cells to 17.5 MeV/u 20 Ne ions (294 keV/µm) are consistent with those to 18.3 MeV/u 12 C and 13.0 MeV/u 20 Ne ions. We also demonstrate that such bystander-induced reductions in the survival are less pronounced and occur independently of Bcl-2 overexpression in human cervical cancer HeLa cells.

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Heavy-Ion Microbeam System at JAEA-Takasaki for Microbeam Biology

Cited by 62 publications

References 42 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 correlation of long term effects and radiation quality in the progeny of bystander cells after microbeam radiations: The experimental study of radiotherapy for cancer risk mitigation

Heavy-Ion Microbeam Irradiation Induces Bystander Killing of Human Cells

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