Cell cycle arrest and apoptosis in<i>Caenorhabditis elegans</i>germline cells following heavy-ion microbeam irradiation

Sugimoto, Tomoko; Dazai, Kumiko; Sakashita, Tetsuya; Funayama, Tomoo; Wada, Seiichi; Hamada, Nobuyuki; Kakizaki, Takehiko; Kobayashi, Yasuhiko; Higashitani, Akihiro

doi:10.1080/09553000600577821

Cited by 48 publications

(41 citation statements)

References 19 publications

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“…These results show that similar egg-lethal effects of high energy carbon ions occur before and after hatching, and that high-LET radiation does not additionally induce lethal effects on eggs in the body of C. elegans. This may support the hypothesis that the bystander effect is little if any in the last stage of embryogenesis of germ-line in C. elegans (Sugimoto et al, 2006), although the bystander-induced expression of heat-shock protein HSP-4 was reported (Bertucci et al, 2009). Taken together, we found that eggs of C. elegans were more sensitive to high-LET radiation exposure than to low-LET radiation exposure.…”

Section: Dose Response For Hatchabilitysupporting

confidence: 78%

“…− 9 − findings imply that DNA damage induced by high-LET radiation underlie high RBE for hatchability in C. elegans. The hatchability observed in this study is very close to its previously reported values in eggs laid from 0 -4 h following the whole-body high-LET irradiation of young adult C. elegans (Sugimoto et al, 2006). These results show that similar egg-lethal effects of high energy carbon ions occur before and after hatching, and that high-LET radiation does not additionally induce lethal effects on eggs in the body of C. elegans.…”

Section: Dose Response For Hatchabilitysupporting

confidence: 76%

“…Especially, high-LET radiation at about 100 keV/µm has the greatest biological effects . Microbeam irradiation of high energy carbon ions induced apoptosis in germ cells of C. elegans (Sugimoto et al, 2006). These Hatchability (%) Dose (Gy) Fig.…”

Section: Dose Response For Hatchabilitymentioning

confidence: 99%

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Behavioral Resistance of Caenorhabditis elegans Against High-LET Radiation Exposure

et al. 2012

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Effects of high linear energy transfer (LET) radiation on the functions of the nervous system is a potential risk in interplanetary manned space missions. However, little is known about how the ner vous system is protected against high-LET radiation exposure. The analysis of high-LET radiation resistant animals would be therefore important for space missions. Here, we investigated the resistance to high-LET radiation exposure for two behaviors of the nematode, Caenorhabditis elegans, which is known as a model organism for the nervous system. Tested behaviors were locomotion and chemotaxis to NaCl. In addition, egg hatchability was examined as an indicator of high-LET radiation sensitivity. Relative biological effectiveness (RBE) of high-LET radiation ( 12 C, 18.3 MeV/u, LET = 113 keV/ µm) relative to low-LET radiation for hatchability was 4.5, whereas RBEs for locomotion and chemotaxis were 1.4 and 1.1, respectively. This study shows that the behavioral system for locomotion and chemotaxis of C. elegans is highly resistant to high-LET radiation exposure.

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Section: Dose Response For Hatchabilitysupporting

confidence: 78%

Section: Dose Response For Hatchabilitysupporting

confidence: 76%

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Behavioral Resistance of Caenorhabditis elegans Against High-LET Radiation Exposure

et al. 2012

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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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“…1) was immersed in 70% ethanol bath for 1 h, exposed to UVC light for 3 h, and then used for cell inoculation. Considering that roughly 80% of the particle fluence collimated through a 20-µm-diameter microaperture was confined to the area of central 20-µm circle around which the remaining 20% was scattered to the area of 15-µm-wide annulus (Sugimoto et al, 2006), we refer to the unit of the target number herein as the site, rather than the cell. For all the experiments, 10 particles of three different types of heavy ions (physical properties listed in Table 1) were delivered to each of 1, 5 and 25 sites with a matrix distribution of 3 mm x 3 mm area in the center of the dish .…”

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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Cell cycle arrest and apoptosis inCaenorhabditis elegansgermline cells following heavy-ion microbeam irradiation

Cited by 48 publications

References 19 publications

Behavioral Resistance of Caenorhabditis elegans Against High-LET Radiation Exposure

Behavioral Resistance of Caenorhabditis elegans Against High-LET Radiation Exposure

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

Heavy-Ion Microbeam Irradiation Induces Bystander Killing of Human Cells

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