Refine your search:     
Report No.
 - 
Search Results: Records 1-20 displayed on this page of 373

Presentation/Publication Type

Initialising ...

Refine

Journal/Book Title

Initialising ...

Meeting title

Initialising ...

First Author

Initialising ...

Keyword

Initialising ...

Language

Initialising ...

Publication Year

Initialising ...

Held year of conference

Initialising ...

Save select records

Journal Articles

The Role of nitric oxide in radiation-induced bystander cell-killing effect

Yokota, Yuichiro; Funayama, Tomoo; Ikeda, Hiroko; Sakashita, Tetsuya; Suzuki, Michiyo; Kobayashi, Yasuhiko

JAEA-Review 2015-022, JAEA Takasaki Annual Report 2014, P. 67, 2016/02

The role of nitric oxide (NO) in bystander effect was investigated. Human fibroblasts were irradiated with $$gamma$$-rays (LET: 0.2 keV/$$mu$$m) or carbon-ion beam (108 keV/$$mu$$m), and then, co-cultured with the non-irradiated cells. After 24 h culture, the survival rates of non-irradiated cells and the concentrations of nitrate, an oxide of NO, in the medium were measured. The survival rates of non-irradiated cells decreased in dose-dependent and radiation quality-independent manners. Negative relationships between survival rates and nitrite concentrations existed, indicating the amounts of produced NO are an important determinant of bystander effects. Next, a reagent producing two molecules of NO in a half-life of 100 min was added in the culture medium. After incubation of 24 h the survival rates of treated cells did not decrease, suggesting NO produced intracellularly has an important role to lead the bystander effect but is not the signal molecule for intercellular communication.

Journal Articles

Characteristics of radiation-induced bystander effect; Participation of nitric oxide

Yokota, Yuichiro; Funayama, Tomoo; Ikeda, Hiroko; Kobayashi, Yasuhiko

Isotope News, (741), p.21 - 25, 2016/01

Our article published on the International Journal of Radiation Biology (2015) was reviewed. We investigated the dependence of the bystander cell-killing effect on radiation dose and quality, and related molecular mechanisms. Human fibroblasts were irradiated with $$gamma$$-rays or carbon ions and co-cultured with non-irradiated cells. Survival rates of non-irradiated cells decreased and nitrite concentrations in co-culture medium increased with dose. Their dose responses were similar between $$gamma$$-rays and carbon ions. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of non-irradiated cells. Negative relationships were observed between survival rates and nitrite concentrations. From these results, it was concluded that the bystander cell-killing effect mediated by NO radicals depends on irradiation doses, but not on radiation quality. NO radical production appears to be an important determinant of bystander effects.

Journal Articles

A Mathematical model of radiation-induced responses in a cellular population including cell-to-cell communications

Hattori, Yuya; Suzuki, Michiyo; Funayama, Tomoo; Kobayashi, Yasuhiko; Yokoya, Akinari; Watanabe, Ritsuko

Radiation Protection Dosimetry, 166(1-4), p.142 - 147, 2015/09

 Times Cited Count:3 Percentile:53.75(Environmental Sciences)

Cell-to-cell communication is one of the important factors to understand the mechanisms of radiation-induced responses such as radiation-induced bystander effects at low doses. In the present study, we propose simulation-based analyses of the intercellular signal transmissions between the individual cells in the cellular population. We developed the transmissions of two types of signals, i.e., X is transmitted via culture medium and Y is transmitted via gap junctions based on the diffusion equation. To observe the cell cycle as the response of cell induced by the signals, X and Y, we represented the cell cycle as a virtual clock including several check-point pathways and the cyclic process (G1, S, G2, M phases). The cellular population was divided into the grids (cells), and the signals and the clock were calculated for each grid. The signals, X, Y, were transmitted to the cells and stopped the clocks at the check points. Furthermore, the radiation was modeled as the radiation signal, Z, which affected the clock and the signals, X and Y. We input the radiation signal, Z, to specific cells, and simulated the behaviors of the clock of each cell and signals, X and Y. We will discuss the usefulness of our model for investigating the mechanisms of radiation-induced responses of the cell cycle via cell-to-cell communications.

Journal Articles

Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation

Tomita, Masanori*; Matsumoto, Hideki*; Funayama, Tomoo; Yokota, Yuichiro; Otsuka, Kensuke*; Maeda, Munetoshi*; Kobayashi, Yasuhiko

Life Sciences in Space Research, 6, p.36 - 43, 2015/07

A radiation-induced bystander response is generally known as a cellular response induced in unirradiated cell by receiving bystander signaling factors released from directly irradiated cells of a cell population. Bystander responses induced by high-LET heavy ions at low fluence are an important problem concerning the health of astronauts in the space environment. Here we set out NO-mediated bystander signal transductions induced by high-LET heavy-ion microbeam irradiation in normal human fibroblasts. Our findings suggest that Akt- and NF-$$kappa$$B-dependent signaling pathway involving COX-2 plays an important role in the NO-mediated high-LET heavy-ion-induced bystander responses. Additionally, COX-2 may be used as a molecular marker of high-LET heavy-ion-induced bystander cells, which are distinguish form directly irradiated cells.

Journal Articles

The Bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality

Yokota, Yuichiro; Funayama, Tomoo; Muto, Yasuko*; Ikeda, Hiroko; Kobayashi, Yasuhiko

International Journal of Radiation Biology, 91(5), p.383 - 388, 2015/05

 Times Cited Count:5 Percentile:34.97(Biology)

We investigated the dependence of the bystander cell-killing effect on radiation dose and quality, and related molecular mechanisms. Human fibroblasts were irradiated with $$gamma$$-rays or carbon ions and co-cultured with non-irradiated cells. Survival rates of non-irradiated cells decreased and nitrite concentrations in culture medium increased with increasing doses. Their dose responses were similar between $$gamma$$-rays and carbon ions. Treatment of the specific nitric oxide (NO) radical scavenger prevented reductions in survival rates of non-irradiated cells. Negative relationships were observed between survival rates and nitrite concentrations. From these results, it was concluded that the bystander cell-killing effect mediated by NO radicals in human fibroblasts depends on irradiation doses, but not on radiation quality. NO radical production appears to be an important determinant of $$gamma$$-ray- and carbon-ion-induced bystander effects.

Journal Articles

Responses of the salt chemotaxis learning in ${it C. elegans}$ mutants to microbeam irradiation

Sakashita, Tetsuya; Suzuki, Michiyo; Hattori, Yuya; Ikeda, Hiroko; Muto, Yasuko*; Yokota, Yuichiro; Funayama, Tomoo; Hamada, Nobuyuki*; Shirai, Kana*; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 74, 2015/03

An increasing body of data indicates that ionizing radiation affects the nervous system and alters its function. Recently, we reported that chemotaxis of ${it C. elegans}$ during the salt chemotaxis learning (SCL), that is conditioned taste aversion to NaCl, was modulated by carbon ion irradiation, i.e. accelerated decrease in chemotaxis to NaCl during the SCL. However, we had no direct evidence for the interaction of ionizing radiation with the central neuronal tissue (nerve ring) in ${it C. elegans}$. Microbeam irradiation is useful to analyze direct radiation effects at a cellular or tissue level. Thus, we applied the microbeam irradiation of the ${it C. elegans}$ nerve ring and examined the effect on the SCL.

Journal Articles

Effect of ionizing radiation upon dehydrated Pv11 cultured cells originated from the sleeping chironomid

Watanabe, Kazuyo*; Akitsuki, Takashi*; Shimura, Sachiko*; Gusev, O.*; Cornette, R.*; Kikawada, Takahiro*; Sakashita, Tetsuya; Funayama, Tomoo; Kobayashi, Yasuhiko; Okuda, Takashi*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 87, 2015/03

The Sleeping Chironomid, ${it Polypedilum vanderplanki}$ can stand complete desiccation (anhydrobiosis) and also shows radio-resistance. Recently, we have generated cultured cell (Pv11) originated from ${it P. vanderplanki}$ embryo which can also stand complete dehydration. In this study, we examine the tolerance of cultured cell Pv11 against ionbeam irradiation.

Journal Articles

Effects of carbon-ion microbeam irradiation on locomotion and pharyngeal pumping motion in $textit{C. elegans}$

Suzuki, Michiyo; Hattori, Yuya; Sakashita, Tetsuya; Funayama, Tomoo; Yokota, Yuichiro; Ikeda, Hiroko; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 88, 2015/03

Journal Articles

Bystander effect mediated by nitric oxide depends on irradiation dose but not on radiation quality

Yokota, Yuichiro; Funayama, Tomoo; Ikeda, Hiroko; Sakashita, Tetsuya; Suzuki, Michiyo; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 75, 2015/03

We investigated the bystander effect induced by $$gamma$$-rays or carbon ions and analyzed the role of nitric oxide (NO) in the effect. Normal human fibroblasts were used. Cells inoculated on a porous membrane were irradiated with varying doses of $$gamma$$-rays or carbon ions. Irradiated cells were then non-contact co-cultured with non-irradiated cells for 24 h. After co-culture, the survival rates of non-irradiated bystander cells co-cultured with irradiated cells decreased with increasing dose and bottomed out at 0.5 Gy or higher doses. This indicates that the bystander effect is dependent on irradiation dose but independent of radiation quality. Next, a specific NO scavenger c-PTIO was added to the culture medium during irradiation and co-culture. This treatment prevented the reduction in survival rates of bystander cells, clearly indicating that NO has an important role in the bystander effect.

Journal Articles

Target irradiation of individual cells using focusing heavy-ion microbeam of JAEA-Takasaki, 5; Irradiation of individual cells with scanned heavy-ion microbeam

Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 73, 2015/03

Using a collimating heavy-ion microbeam system, we have explored various effects of heavy-ion hit on biological materials. However, there are limitations of the collimating system in the size of the microbeam spot and in the irradiation speed that cannot be overcome in principle. Thus, we started the development of a focusing microbeam system for target-irradiating individual cells more precisely. In this year, we established the protocol for irradiating "actual" cell sample with scanned beam. In the experiment, the HeLa cells were inoculated on a CR-39 film, then place on the sample stage. The microscopic image of cells was analyzed, and the cells were irradiated with scanned neon microbeam. After irradiation, we found the correspondence of the distribution pattern of the ion hit positions and the $$gamma$$-H2AX foci on cell nuclei, indicating rapid and accurate irradiation of individual cells with the focusing heavy-ion microbeam.

Journal Articles

Mechanisms for the induction of radioadaptive response by radiation-induced bystander response

Matsumoto, Hideki*; Tomita, Masanori*; Otsuka, Kensuke*; Hatashita, Masanori*; Maeda, Munetoshi*; Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Ikeda, Hiroko; et al.

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 76, 2015/03

The objective of this project is to elucidate molecular mechanisms for the induction of radioadaptive response through radiation-induced bystander responses induced by irradiation with heavy ion microbeams in JAEA. We found that the adaptive response was induced by Ar (520 MeV $$^{40}$$Ar$$^{14+}$$) microbeam-irradiation of a limited number of cells, followed by the broad beam-irradiation and that the adaptive response was almost completely suppressed by the addition of carboxy-PTIO, as a nitric oxide (NO) scavenger. In addition, we found several genes induced specifically and preferentially when radioadaptive response could be induced. We confirmed that ${it iNOS}$ expression was specifically induced only when radioadaptive response could be induced. Our findings strongly suggested that radioadaptive response can be induced by NO-mediated bystander responses evoked by irradiation with heavy ion microbeams.

Journal Articles

Analysis of bystander response in 3D cultured tissue induced by heavy-ion microbeam irradiation

Tomita, Masanori*; Matsumoto, Hideki*; Otsuka, Kensuke*; Funayama, Tomoo; Yokota, Yuichiro; Suzuki, Michiyo; Sakashita, Tetsuya; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 77, 2015/03

Radiation-induced bystander responses are defined as responses in cells that have not been directly targeted by radiation but are in the neighborhood of cells that have been directly exposed. In this study, we aim to clarify a role of bystander response to sustain the homeostasis of damaged tissue using heavy-ion microbeams. We established the heavy-ion microbeam irradiation method to a 3D cultured human epidermis. Using this method, a viable cell rate of the 3D cultured human epidermis irradiated with 260 MeV $$^{20}$$Ne-ion microbeams or broadbeams was analyzed by the MTT method.

Journal Articles

Ion-species dependent bystander mutagenic effect on ${it HPRT}$ locus in normal human fibroblasts induced by C-, Ne- and Ar-ion microbeams

Suzuki, Masao*; Funayama, Tomoo; Yokota, Yuichiro; Muto, Yasuko*; Suzuki, Michiyo; Ikeda, Hiroko; Hattori, Yuya; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 78, 2015/03

We have been studying the radiation-quality dependent bystander cellular effects, such as cell killing, mutation induction and chromosomal damage, using heavy-ion microbeams with different ion species. This year we focused on the ion-species dependent bystander mutagenic effect on ${it HPRT}$ locus in normal human fibroblasts. The confluent culture were irradiated using a 256 (16$$times$$16)-cross-stripe method using C, Ne and Ar microbeam. Gene mutation on ${it HPRT}$ locus was detected with 6-thioguanine resistant clones. The mutation frequency in cells irradiated with C-ion microbeams was 6 times higher than that of non-irradiated control cells and of the sample treated with specific inhibitor of gap-junction cell-to-cell communication. On the other hand, no enhanced mutation frequencies were observed in cells irradiated with either Ne- or Ar-ion microbeams. There is clear evidence that the bystander mutagenic effect via gap-junction communication depends on radiation quality.

Journal Articles

Analysis of bystander effect induced by cell membrane response in glioma cells

Wada, Seiichi*; Ando, Tatsuhiko*; Watanabe, Aya*; Kakizaki, Takehiko*; Natsuhori, Masahiro*; Funayama, Tomoo; Sakashita, Tetsuya; Yokota, Yuichiro; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 79, 2015/03

So far, we clarified that X-ray irradiation induced cell killing by bystander effect mediated-secreted factor. This phenomenon was related with sphingomyelinase (SMase). In this study we analyzed mechanism of secreted SMase from irradiated cells after irradiation. SMase was detected in the culture medium after irradiation by SDS-PAGE. Then, SMase was detected in the exosome of culture medium, but not out of exosome after irradiation. This result indicates that SMase was secreted as exosome from the irradiated cells.

Journal Articles

Ion beam irradiation has different influences on superoxide dismutase activity in cultured human retinal vascular endothelial cells between $$^{12}$$C and $$^{4}$$He

Akeo, Kiyoshi*; Funayama, Tomoo; Kobayashi, Yasuhiko; Akeo, Yoko*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 80, 2015/03

It is known that superoxide dismutases (SOD) are a class of enzymes that catalyze the dismutation of superoxide into oxygen and hydrogen peroxide. Ionizing radiation is known to induce oxidative stress through generation of reactive oxygen species resulting in imbalance of the pro-oxidant and antioxidant in the cells, which is suggested to culminate in cell death. Therefore, we measured the activity of SOD in human RE cells exposed to the He- and C-ion beam. The cells collected at 0, 4, 8, and 24 hr after irradiation were extracted by adding the SOD assay buffer to the pellets, and lysed by several cycles of freezing and thawing. The activity of SOD was measured using a modification of the luminol assay. SOD activity decreased according to duration time after irradiation of He-ion, however, in case of C-ion, it increased at 24 hr after irradiation. The result suggested that that there were the differences of the effects by irradiation on SOD activity between He- and C-ion.

Journal Articles

Effect of heavy ion irradiation to the silkworm eggs at before fertilization and at nuclear cleavage stage

Ueda, Daisuke*; Shirai, Koji*; Funayama, Tomoo; Sakashita, Tetsuya; Yokota, Yuichiro; Kobayashi, Yasuhiko

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 84, 2015/03

In this study, we investigated the effects of irradiation to the silkworm eggs at various developmental stages. First, we tried the irradiation to the unfertilized eggs (at 1.5 hour after oviposition). At this stage, the female pronucleus and the sperm nucleus are observed in the eggs, but not fertilized. After irradiation, the irradiated eggs stopped the development after fertilization. About 2 hours after, the egg restarted the nuclear cleavage. This result indicates the DNA damage on pronuleus cannot prevent the fertilization. We also investigated the effects of irradiation to the egg at the nuclear cleavage stage (at 6 hour after oviposition). The egg also stopped the development after irradiation, but the duration time of the developmental arrest was almost two times longer (about 4 hours) than that of the egg irradiated at fertilization.

Journal Articles

Medaka blastoderm cells are capable of compensating the injured cells irradiated by carbon-ion micro-beam

Yasuda, Takako*; Oda, Shoji*; Asaka, Tomomi*; Funayama, Tomoo; Yokota, Yuichiro; Muto, Yasuko*; Ikeda, Hiroko; Kobayashi, Yasuhiko; Mitani, Hiroshi*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 85, 2015/03

In this present study, we examined the effects of heavy carbon-ions on development in pre-implantation period utilizing medaka blastula stage embryos (st. 11: blastderm diameter is about 500 $$mu$$m). We performed targeted irradiation by carbon-ion micro-beam (diameters of 120, 180 $$mu$$m) to a central parts of blastoderm and observed the abnormalities during development compared with whole-body irradiated embryos. As a results, retardation and characteristic malformed eyes were observed during development when blastoderm cells were partially irradiated, However, more than half of 50 Gy-irradiated embryos (area size=120 $$mu$$m diameter) could hatch normally in contrast to all embryos with 2 Gy of whole-body irradiation being lethal before hutching.

Journal Articles

LET dependency of human normal dermal cells survival in carbon ion irradiation

Yoshida, Yukari*; Mizohata, Kensuke*; Matsumura, Akihiko*; Isono, Mayu*; Yako, Tomoko*; Nakano, Takashi*; Funayama, Tomoo; Kobayashi, Yasuhiko; Kanai, Tatsuaki*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 81, 2015/03

In the clinical application of carbon-ion (C-ion) radiation therapy in Japan, different RBE values of carbons have been used for clinical and biological endpoints. The biological RBE (bRBE) was estimated by a method that is based on the linear-quadratic (LQ) model, and was defined ${it in vitro}$ at the 10% surviving fraction of human salivary gland (HSG) tumor cells. However, many of biological parameters, that is, type of tissues, different sort of cells, oxygenation levels, and all, could affect radiosensitivity. Thus, normal human dermal fibroblasts (NHDF) cells were exposed to C-ion beams at Gunma University (10-80 keV/micrometer) and TIARA (108 and 158 keV/micrometer). The surviving fractions were analyzed with colony formation assays. The experimental RBE (eRBE) values were estimated from the radiation dose survival curve fitted by LQ model, and defined ${it in vitro}$.

Journal Articles

NHEJ repair rather than HR repair is the primary function to target to enhance radiosensitization at high LET values

Takahashi, Akihisa*; Kubo, Makoto*; Igarashi, Chie*; Yoshida, Yukari*; Funayama, Tomoo; Kobayashi, Yasuhiko; Nakano, Takashi*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 82, 2015/03

DNA double-strand breaks (DSBs) induced by ionizing radiation pose a major threat to cell survival. The cell can respond to the presence of DSBs, through two major repair pathways: Homologous recombination (HR) and non-homologous end-joining (NHEJ). Higher levels of cell death are induced by high-LET radiation when compared to low-LET radiation, even at the same doses because of less effective or more inefficient DNA repair. In this study, we examine the effects of radiation with different LET values on DNA DSB repair and radiosensitivity. Wild-type cells and HR deficient (but NHEJ proficient) cells exhibited the high RBE values at LET values of 108 keV/$$mu$$ m. The RBE value for each cell type decreased with increasing LET values over 200 keV/$$mu$$m. Although NHEJ proficient cells had an almost constant SER value, NHEJ deficient cells showed a high SER value when compared to NHEJ proficient cells, even with increasing LET values.

Journal Articles

Epigenetic modifier as a potential radiosensitizer for heavy-ion therapy on malignancy, 2

Saito, Katsuyo*; Funayama, Tomoo; Kobayashi, Yasuhiko; Murakami, Takashi*

JAEA-Review 2014-050, JAEA Takasaki Annual Report 2013, P. 83, 2015/03

Epigenetic modifiers, such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors, have emerged recently as promising anticancer agents and it has been expected that epigenetic modifiers may enhance the effect of other cancer therapeutics including radiotherapy. Therefore, we investigated whether the use of epigenetic modifiers could sensitize melanoma cells for the heavy-ion therapy. Murine B16F10 melanoma cells were treated with investigational or comparator epigenetic modifier, then exposed to carbon ions of JAEA-Takasaki. After irradiation, the viabilities of cells were evaluated by colony formation assay. Treatment of B16F10 melanoma cells with HDACi trichostatin A (TSA) in combination with heavy-ion radiation provided enhanced inhibition of colony formation. The data suggest that combination of an epigenetic modifier TSA together with heavy-ion therapy may provide improved therapeutic responses in melanoma patients.

373 (Records 1-20 displayed on this page)