Journal of Radiation Research
Online ISSN : 1349-9157
Print ISSN : 0449-3060
Volume 52, Issue 3
Displaying 1-20 of 20 articles from this issue
Regular Papers
  • Yuka ISHIDA, Yasushi OHMACHI, Nobuhiko TAKAI, Takeshi HIRAOKA, Toshiak ...
    2011 Volume 52 Issue 3 Pages 257-263
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: March 16, 2011
    JOURNAL FREE ACCESS
    Epidemiological studies have revealed that radiation causes brain development abnormalities in atomic bomb survivors exposed in utero. Rat and mouse studies have also shown that prenatal exposure to low-linear energy transfer radiation induces developmental brain anomalies. Because the effects of prenatal irradiation on adult behavior patterns remain largely unknown, the present study investigated the effects of neutron exposure in utero on postnatal behavior patterns in mice. [C57BL/6J × C3H/He] hybrid (B6C3F1) mice were exposed to cyclotron-derived fast neutrons with peak energy of 10 MeV (0.02–0.2 Gy) or Cs-137 gamma-rays (0.2–1.5 Gy) on embryonic day 13.5. At 5.5–8 months of age, the neurobehavior of male offspring was examined by Rota-rod treadmill and locomotor activity. The accumulation of radio-labeled drug at muscarinic acetylcholine and serotonin receptors in mice from control and neutron-irradiated groups was determined by the tracer method. Locomotor activity during the dark period increased in the 0.02 Gy neutron-irradiated group. Furthermore, at 5.5 months of age, tracer binding in vivo to the muscarinic acetylcholine increased and to the serotonin receptors decreased in the 0.02 Gy neutron-irradiated group. In conclusion, the present study reveals that a certain "low-dose window" may exist for radiation-induced changes in neurobehavior and binding to neurotransmitter receptors, because there was correlation in neurobehavior and binding to neurotransmitter receptors in the 0.02 Gy neutron-irradiated group though there was not correlation in the neutron-irradiated groups more than 0.05 Gy.
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  • Katsuyuki SHIRAI, Yoshio TAMAKI, Yoshizumi KITAMOTO, Takeo TAKAHASHI, ...
    2011 Volume 52 Issue 3 Pages 264-269
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: February 19, 2011
    JOURNAL FREE ACCESS
    Despite the wide use of definitive chemoradiotherapy (CRT) for locally advanced esophageal adenocarcinoma, there is little evidence that CRT improves the survival of patients with esophageal adenocarcinoma compared with radiotherapy (RT) alone. Therefore, we retrospectively evaluated the outcome of patients with esophageal adenocarcinoma treated by CRT and RT alone. Patients were treated at the Gunma Prefectural Cancer Center (Ota, Japan) and the Gunma University Hospital (Maebashi, Japan). Patients provided written informed consent before treatment. Patients with distant metastases were excluded. CRT consisting of RT, nedaplatin, and 5-fluorouracil has been performed since 2002 when patients have adequate bone marrow, liver, and renal function. Between November 1993 and April 2006, 8 patients were treated by CRT and 12 were RT alone. The median follow-up period of surviving patients was 19 months. CRT group had a significantly higher complete response rate than those RT alone group (87% vs. 33%, P = 0.05). Of all patients, 2-year overall survival rate was 41% and the median survival time was 18 months. The 2-year overall survival of patients treated by CRT was 58%, significantly better than 24% of those with RT alone (P = 0.02). CRT can improve outcomes of patients with esophageal adenocarcinoma compared with RT alone.
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  • Tomoko SAITO-FUJITA, Mayumi IWAKAWA, Etsuko NAKAMURA, Miyako NAKAWATAR ...
    2011 Volume 52 Issue 3 Pages 270-277
    Published: 2011
    Released on J-STAGE: May 31, 2011
    JOURNAL FREE ACCESS
    There is a great deal of evidence that a cyclic cascade of inflammatory cytokines, together with the activation of macrophages, is initiated very early after irradiation to develop lung fibrosis in a late phase. To understand the persistent effects of cytokines, the cytokine gene of knock out or transgenic mouse is one of the useful tools. In this study, we evaluated a role of a key molecule, interleukin-6 (IL-6), in the late-phase inflammatory response and subsequent fibrotic changes after irradiation using wild-type (WT) and IL-6 knock out (IL-6 KO) mice. The mice underwent thoracic irradiation with 10 Gy of C-ion beam or sham-irradiation and were examined by histology. Immunoreactivity for IL-6 was induced at the site of bronchiolar epithelium, in pneumocytes and in monocytes by C-ion irradiation. At 24 weeks after irradiation, the infiltration of macrophages, detected by positive immunohistological staining with Mac3 antibody, was observed in alveolar spaces both in WT and IL-6 KO mice. The thickening of bronchiolar and alveolar walls exhibited in WT mice, but not KO mice, and fibrotic changes detected by Masson-Trichrome staining, were observed only in the lungs of WT mice, while it was attenuated in IL-6 KO mice. These results indicated that IL-6 might not be essential for activating macrophages in the late phase, but plays an important role for fibrotic changes of the alveolar wall after irradiation.
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  • Tomohisa HIROBE, Kiyomi EGUCHI-KASAI, Kimihiko SUGAYA, Masahiro MURAKA ...
    2011 Volume 52 Issue 3 Pages 278-286
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: February 19, 2011
    JOURNAL FREE ACCESS
    Effects of prenatal low-dose irradiations of heavy ions on the postnatal development of mice and of melanocytes have not been well studied. Pregnant females of C57BL/10J mice were irradiated whole-body at 9 days of gestation with a single acute dose of γ-rays, silicon (Si, 57 keV/μm), argon (Ar, 100 keV/μm) and iron (Fe, 220 keV/μm) ions. The effects were studied by scoring changes in the postnatal development of mice as well as in the pigmentation of cutaneous coats and tail-tips of their offspring 22 days after birth. The survival to day 22 decreased from the offspring exposed to 0.4 Gy of argon and iron ions and to 0.75 Gy of silicon ions. White spots were found in the mid-ventrum and tail-tips of irradiated offspring. The frequency and size of the white spots in the mid-ventrum in mice exposed to silicon, argon and iron ions were greater than those of γ-rays. Even in the low dose (0.1 Gy), γ-rays and heavy ions increased the frequency of the ventral spots. The RBE estimated by the frequency of the ventral spots was 2.3 (Si), 3.1 (Ar) and 4.5 (Fe). These results suggest that prenatal exposure to heavy ions possesses a greater effect on the postnatal development of mice as well as melanocyte development than does exposure to γ-rays.
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  • Hiroki KIYOHARA, Yasuki ISHIZAKI, Yoshiyuki SUZUKI, Hiroyuki KATOH, No ...
    2011 Volume 52 Issue 3 Pages 287-292
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: February 19, 2011
    JOURNAL FREE ACCESS
    Adhesion of inflammatory cells to endothelial cells is considered to be involved in the process of radiation-induced damage and fibrosis. Intercellular adhesion molecule-1 (ICAM-1) and transforming growth factor-beta1 (TGF-β1) are thought to play important roles in this process. In this study, radiation-induced ICAM-1 expression on endothelial cells was investigated with the use of an inhibitor of TGF-β1 receptor kinase (SB431542) and the effects of X-ray and carbon-ion beam were compared. Cell cultures of human umbilical vein endothelial cells (HUVE cells) were incubated with TGF-β1 and irradiated with 140 KV X-ray. Next, HUVE cells were irradiated with X-ray and 220 MeV carbon-ion beam with or without SB431542. Immunofluorescence analysis was used to quantify ICAM-1 expression. The expression of ICAM-1 on HUVE cells was significantly increased by the stimulation with TGF-β1. Expression of ICAM-1 was increased by X-ray and carbon-ion beam irradiation and decreased significantly with SB431542 after both irradiations. The expression of ICAM-1 by 2 Gy of carbon-ion beam irradiation was 6.7 fold higher than that of non-irradiated cells, while 5 Gy of X-ray irradiation increased the expression of ICAM-1 by 2.5 fold. According to ICAM-1 expression, the effect of carbon-ion beam irradiation was about 2.2, 4.4 and 5.0 times greater than that of the same doses of X-ray irradiation (1, 2 and 5 Gy, respectively). The present results suggested that radiation-induced ICAM-1 expression on HUVE cells was, at least partially, regulated by TGF-β1. Carbon-ion beam induced significantly higher ICAM-1 expression than X-ray.
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  • Kengo KATO, Mikinori KUWABARA, Ikuo KASHIWAKURA
    2011 Volume 52 Issue 3 Pages 293-299
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: March 31, 2011
    JOURNAL FREE ACCESS
    To investigate the importance of gender and aging on the individual radiosensitivity of lineage-committed myeloid hematopoietic stem/progenitor cells (HSPCs) detected in mononuclear cells (MNCs) of steady-state human peripheral blood (PB), the clonogenic survival of HPCs, including colony-forming unit-granulocyte macrophage; burst-forming unit-erythroid; colony-forming unit-granulocyte-erythroid-macrophage-megakaryocyte cells derived from MNCs exposed to 0.5 Gy and 2 Gy X-irradiation were estimated. MNCs were prepared from the buffy-coats of 59 healthy individual blood donors. The results showed that large individual differences exist in the number of HSPCs, as well as in the surviving fraction of cells. Furthermore, the number of progenitor cells strongly correlated with their surviving fraction, suggesting that the radiosensitivity of hematopoietic progenitor cells decreases with the number of cells in the 105 cells population. A statistically significant negative correlation was observed between the surviving fraction observed at a dose of 0.5 Gy and the age of an individual, however, none of these correlations were observed after 2 Gy irradiation. No statistically significant difference was observed in individual radiosensitivity between males and females at either radiation dose. The present results indicated a correlation between the individual responsiveness of HSPCs to ionizing irradiation, especially to low dose irradiation, and aging.
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  • Natalia SUMPTION, Liz AINSBURY, Dudley GOODHEAD, Toshiyuki HIRAMA, Mak ...
    2011 Volume 52 Issue 3 Pages 300-308
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: April 23, 2011
    JOURNAL FREE ACCESS
    In September 1999 a criticality accident occurred in a uranium processing plant in Tokai-mura, Japan. During the accident, three workers (A, B and C) were exposed to high acute doses of neutrons and γ-rays: workers A and B fatally and worker C to an estimated whole body absorbed dose of 0.81 Gy neutrons and 1.3 Gy γ-rays. We obtained fixed peripheral blood lymphocytes (PBL) preparations from worker C approximately four and five years after the accident and assayed by 24 colour karyotyping (M-FISH) to determine the frequency and complexity of chromosome aberrations present. We observed a high frequency of simple reciprocal translocations, which we used to provide a rough estimation of dose and, in addition, for the assessment of the emergence of any clinically-relevant clonal exchanges. We did not observe any evidence of clonality but did find some evidence suggesting chromosome 1 as being preferentially involved in exchanges in stable cells. We also detected a relatively high frequency of damaged cells containing complex chromosome aberrations, of both the stable and unstable types. Qualitatively these complex aberrations were consistent with those observed to be induced after exposure to low doses of high-LET radiation or moderate doses of low-LET radiation, supporting the suggestion that heavily damaged cells can be quite long-lived in vivo.
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  • Dalong PANG, Thomas A. WINTERS, Mira JUNG, Shubhadeep PURKAYASTHA, Luc ...
    2011 Volume 52 Issue 3 Pages 309-319
    Published: 2011
    Released on J-STAGE: May 31, 2011
    JOURNAL FREE ACCESS
    Cells exposed to densely ionizing radiation (high-LET) experience more severe biological damage than do cells exposed to sparsely ionizing radiation (low-LET). The prevailing hypothesis is that high-LET radiations induce DNA double strand-breaks (DSB) that are more complex and clustered, and are thereby more challenging to repair. Here, we present experimental data obtained by atomic force microscopy imaging, DNA-dependent protein kinase (DNA-PK) activity determination, DNA ligation assays, and genomic studies to suggest that short DNA fragments are important products of radiation-induced DNA lesions, and that the lengths of DNA fragments may be significant in the cellular responses to ionizing radiation. We propose the presence of a subset of short DNA fragments that may affect cell survival and genetic stability following exposure to ionizing radiation, and that the enhanced biological effects of high-LET radiation may be explained, in part, by the production of increased quantities of short DNA fragments.
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  • Xiangpeng ZHENG, Sumathy MOHAN, Randal A. OTTO, Mohan NATARAJAN
    2011 Volume 52 Issue 3 Pages 320-328
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: April 23, 2011
    JOURNAL FREE ACCESS
    The response of endothelial cells to radiation in the context of wound healing is not yet completely understood. In this study we investigated the mechanism involved in the wound healing process after low linear energy transfer (LET) radiation exposure. A scratch wound model on primary vascular endothelial cell monolayer was exposed to acute dose of 0.1, 2 or 10 Gy. The number of cells crossing the wound border and the wound closure percentage was measured. The expression of αvβ3 integrins, focal adhesion kinase (FAK) and phosphorylated FAK (tyr397) as well as SHP-2 phosphatase were assayed through immunoblotting, immunoprecipitation and optical imaging. Compared to the low dose irradiation, 2 and 10 Gy had remarkably inhibitory effects on cell motility and consequently the wound closure. Integrins αv and β3 showed no irradiation-dose dependent variation. Contrast to the relatively constant level of FAK in all groups, the amount of phosphor-FAK tyr397 was higher with dose increasing. The protein and PCR analysis of SHP-2 revealed an opposite expression pattern to FAK tyr397. In conclusion, radiation-induced inhibition of cell migration could be attributed to the irradiative inhibition to SHP-2 phosphatase, and the subsequent accumulated phosphorylated FAK abrogated the contraction-extension cycle of cytoskeletons.
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  • Tadayuki KOTSUMA, Ken YOSHIDA, Hideya YAMAZAKI, Tadashi TAKENAKA, Kouj ...
    2011 Volume 52 Issue 3 Pages 329-334
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: March 31, 2011
    JOURNAL FREE ACCESS
    This report presents initial experience with imaging-aided high-dose-rate interstitial brachytherapy (HDR-ISBT) for post-operative recurrence of uterine carcinoma. Fourteen patients presenting with post-operative recurrence of uterine carcinoma (nine cervix and five corpus) between July 2005 and October 2008 were enrolled in this study (median follow-up: 37 months, range: 6–59 months). We implanted magnetic resonance imaging (MRI)-compatible plastic applicators using our own ambulatory technique. HDR-ISBT treatment consisted of twice-a-day irradiation of 6 Gy each with at least a six-hour interval to provide the total prescribed dose. Treatment was based on treatment planning-computed tomography with MRI as a reference. Seven patients were treated with a combination of ISBT (median 30 Gy/5 fractions; range: 27–33 Gy) and external beam radiation therapy (EBRT), and the other seven with brachytherapy only (median 54 Gy/9 fractions; range: 48–54 Gy), one of whom had previously received pelvic EBRT. The three-year estimates of local control and overall survival rates were 77.9% (95% confidence interval (CI): 55.8–100%) and 77.1% (95% CI: 54.2–100%), respectively. Two patients, who had received combined treatment with EBRT showed untoward reactions, including a grade 3 subileus and grade 2 constipation. Another patient, who had been treated with ISBT alone, developed grade 2 urinary constriction. Our imaging-aided HDR-ISBT for post-operative recurrence of uterine carcinoma was found to be practical with promising preliminary results.
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  • Xiaodong JIN, Qiang LI, Qingfeng WU, Ping LI, Yoshitaka MATSUMOTO, Yos ...
    2011 Volume 52 Issue 3 Pages 335-341
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: April 23, 2011
    JOURNAL FREE ACCESS
    In this study, whether survivin plays a direct role in mediating high-LET radiation resistance in human hepatoma cells was investigated. Small interfering RNA (siRNA) targeting survivin mRNA was designed and transfected into human hepatoma HepG2 cells. Real-time PCR and western blotting analyses revealed that survivin expression in HepG2 cells decreased at both transcriptional and post-transcriptional levels after treatment with survivin-specific siRNA. Caspase-3 activity was determined with a microplate reader assay as well. Following exposure to high-LET carbon ions, a reduced clonogenic survival effect, increased apoptotic rates and caspase-3 activity were observed in the cells treated with the siRNA compared to those untreated with the siRNA. The cells with transfection of the survivin-specific siRNA also increased the level of G2/M arrest. These results suggest that survivin definitely plays a role in mediating the resistance of HepG2 cells to high-LET radiation and depressing survivin expression might be useful to improve the therapeutic efficacy of heavy ions for radioresistant solid tumors.
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  • Azusa ITO, Akinori MORITA, Soichiro OHYA, Shinichi YAMAMOTO, Atsushi E ...
    2011 Volume 52 Issue 3 Pages 342-350
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: March 31, 2011
    JOURNAL FREE ACCESS
    The human T-cell leukemia cell line MOLT-4 is highly radiosensitive, and thus it is often used as a model of p53-dependent radiation-induced apoptosis. Two branches of the p53-mediated apoptotic pathway are reported: "transcription-dependent" and "transcription-independent." However, the relative contribution of each in different types of cells is not yet clearly defined. Moreover, recent studies have shown that the codon 72 polymorphic variants of p53 show different sensitivities to apoptosis signals. The Arg72 variant has a more potent apoptosis-inducing activity in mitochondria than the Pro72 variant. Here, we initially investigated the codon 72 polymorphism of p53 in MOLT-4 cells. Analysis of the p53 exon 4 genomic DNA sequence, which includes codon 72, revealed that MOLT-4 cells are homozygous for the allele encoding Arg72. We next investigated the involvement of the transcription-independent function of p53 using an RNA synthesis inhibitor, actinomycin D (ActD), and a protein synthesis inhibitor, cycloheximide (CHX), and found that the apoptosis was suppressed by CHX but not by ActD. We also revealed that the suppressive effect of CHX on apoptosis was specifically mediated by p53, using a p53-knockdown MOLT-4 transfectant. Furthermore, the suppressive effect of CHX on apoptosis was highly correlated with the suppression of p53 protein accumulation, and less correlated with the suppression of p53 target genes expression. These results indicated that p53 transactivation is not necessary to induce apoptosis, and that p53 protein accumulation itself is both necessary and sufficient to do so.
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  • Kaori SEKI-NAKAMURA, Katsuya MAEBAYASHI, Sachiko NASU-IZUMI, Tetsuo AK ...
    2011 Volume 52 Issue 3 Pages 351-359
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: March 31, 2011
    JOURNAL FREE ACCESS
    We conducted a prospective study to assess the anxiety and salivary Chromogranin A (CgA), which is considered to be a biomarker of the stress response, in outpatients receiving breast conserving surgery followed by radiation therapy (RT) to the whole breast. Fifty consecutive patients who received whole-breast RT were enrolled in this study. The anxiety levels were measured by the State-Trait Anxiety Inventory (STAI) at the beginning of RT (baseline), 30 Gy, completion of RT, and 1 and 3 months after RT. Salivary CgA levels were also measured at the same time. The mean state anxiety score for all patients was 46.16 with a standard error (SE) of 1.57 at the beginning of RT (baseline) which continued to decline during and after RT. It reached its lowest score with 36.34 ± 1.56 at 3 months after RT (p < 0.0001). The mean trait anxiety score for all patients was 43.10 ± 1.54 at baseline and remained constant during RT but began to decline after completion of RT and reached a low level at 3 months after RT (p = 0.0021). The mean salivary CgA concentration for all patients demonstrated no consistent trends over time, but at 30 Gy the concentration showed a significant decreasing pattern (p = 0.0473). Salivary CgA concentrations and state anxiety and trait anxiety scores at all time points showed no correlation. The mean anxiety scores measured by STAI showed no positive correlation with salivary CgA concentration for breast cancer patients undergoing radiation therapy following breast conserving surgery.
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Technical Report
  • Sami HEIKKINEN, Sauli SAVOLAINEN, Petri MELKKO
    2011 Volume 52 Issue 3 Pages 360-364
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: April 23, 2011
    JOURNAL FREE ACCESS
    Supplementary material
    Boron neutron capture therapy (BNCT) is an experimental drug-targeted treatment combining tumour-seeking boronated drug(s) and subsequent 10B activation by neutrons. Synthetic amino acid, L-p-boronophenylalanine (BPA), administered as a fructose complex (BPA-F) is used in BNCT trials. We tested the in vitro biological and structural stability of the BPA-F as a function of time (11 days). The BPA-F samples were analyzed using biological bacterial endotoxin and sterility tests. Visual tests were clarity, degree of opalescence and coloration according to European Pharmacopoeia. The structural stability of the BPA-F was monitored via 1H NMR signal intensity of the aromatic protons of the BPA-F samples. A slight change of BPA-F samples in coloration was observed during storage. BPA-fructose complex remained sterile and bacterial endotoxin tests were negative. In the end of study period, relative intensity of the 1H NMR signals of the BPA-F sample was ≥ 90% of the initial relative intensity. The biological properties of the BPA-fructose complex and chemical structure of the complex remained the same during the test period. Visually the solutions stayed clear, but there was a slight change in colour. The tests indicate that the prepared batch of BPA-F complex can be used for the patient infusion at least for a week.
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Short Communications
  • Shigehiko KURIBAYASHI, Tsuguhiro MIYASHITA, Yukiko OZAWA, Marie IWANO, ...
    2011 Volume 52 Issue 3 Pages 365-368
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: April 14, 2011
    JOURNAL FREE ACCESS
    A study was conducted to evaluate the early results of high-dose-rate superficial brachytherapy (HDR-SB) after keloidectomy. Between April 2008 and April 2009, 21 patients with 36 histologically confirmed keloids were treated with postoperative HDR-SB. The tube applicator was placed on the skin to match the area of the surgical wound, and a spacer 5 mm thick was placed between the skin and the applicator. A dose evaluation point was established below 2 mm from skin surface, and 20 Gy was delivered in 4 daily fractions to keloidectomy scars on the anterior chest wall, scapular region, lower jaw and suprapubic region. A dose of 15 Gy was delivered in 3 daily fractions to lesions in other areas. The median follow-up period was 18 months (range, 9 to 29 months). Therapeutic outcome was judged in terms of recurrence, control, or acute side effects. Three keloids (9.7%) in two patients showed local recurrence, with a median time to failure after HDR-SB of 12 months. All recurrences affected the anterior chest wall. Dysraphia occurred in only one patient with an anterior chest wall lesion. Excluding the cases of recurrence, acceptable cosmetic results were achieved. Our results indicate that HDR-SB is effective and safe for preventing recurrence of keloids.
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  • Mutsumi MATSUU-MATSUYAMA, Kumio OKAICHI, Kazuko SHICHIJO, Toshiyuki NA ...
    2011 Volume 52 Issue 3 Pages 369-373
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: February 19, 2011
    JOURNAL FREE ACCESS
    We previously reported that the apoptosis index in jejunal crypt cells after X irradiation was greater in spontaneously hypertensive rats than in Wistar-Kyoto rats. Moreover, these same cells showed a suppression of apoptosis when reserpine was administered to induce sympathetic dysfunction in spontaneously hypertensive rats or Wistar-Kyoto rats.1) Whether the hyperfunction of the sympathetic nervous system is involved in the high susceptibility of the jejunal crypt cells to radiation-induced apoptosis was the subject of this study. The effect of norepinephrine (NE) on cell survival was examined using the colony formation assay after X-ray irradiation of rat ileal epithelial cells (IEC-18). The addition of 1 μM NE decreased the surviving fraction of cells irradiated with 6 Gy from 37% to 8%. The radiosensitivity of IEC-18 cells was enhanced by the addition of 1 μM of NE. The irradiation and treatment with NE also resulted in an increased cellular apoptotic rate. These results showing enhanced radiosensitivity of rat ileal epithelial cells by NE suggest that NE may be one of the factors which aggravate acute radiation injury in the intestine.
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  • Toshiyuki OGATA, Teruki TESHIMA, Miho INAOKA, Kazumasa MINAMI, Takahir ...
    2011 Volume 52 Issue 3 Pages 374-379
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: February 19, 2011
    JOURNAL FREE ACCESS
    We previously showed that carbon ion irradiation can inhibit the expression of the anillin (ANLN) gene, which is regulated by the activation of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway associated with metastasis. The purpose of this study is to compare the effects of carbon ion irradiation on the PI3K/Akt signaling pathway to those of photon irradiation. Our study showed that carbon ion irradiation of human lung adenocarcinoma cells A549 decreased their invasion more effectively than photon irradiation did. We found that carbon ion irradiation reduced the nuclear localization of ANLN at lower dose, but did not affect its expression. Low-dose carbon ion irradiation also reduced the level of phosphorylated Akt compared to untreated controls, whereas photon irradiation did not. These results suggest that carbon ion irradiation effectively suppresses the metastatic potential of A549 cells by suppressing the PI3K/Akt signaling pathway.
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  • Xinyue LIANG, You Ho SO, Jiuwei CUI, Kewei MA, Xiaoyi XU, Yuguang ZHAO ...
    2011 Volume 52 Issue 3 Pages 380-386
    Published: 2011
    Released on J-STAGE: May 31, 2011
    Advance online publication: March 24, 2011
    JOURNAL FREE ACCESS
    Hormesis induced by low-dose ionizing radiation (LDIR) is often mirrored by its stimulation of cell proliferation. The mitogen-activated protein kinases (MAPK)/ extracellular-signal- regulated kinases (ERK) pathway is known to play important roles in cell growth. Therefore, this study was to examine the effects of LDIR on rat mesenchymal stem cell (MSC) proliferation and MAPK/ERK signaling pathway. Rat MSCs were isolated from the bone marrow from 6 to 8-week-old male Wistar rats and cultured in vitro. Exponentially growing cells within 4–5 passages were irradiated with low doses of X-rays at 20, 50, 75 and 100 mGy with a dose rate of 100 mGy/min. Cell proliferation was evaluated by counting total viable cell number with trypan-blue staining and MTT assay. Cell cycle changes were also evaluated by flow cytometry and the activation of MAPK/ERK signaling pathway was assayed by Western blotting. Results showed that LDIR at 50 and 75 mGy significantly stimulated the proliferation of rat MSCs with the most stimulating effect at 75 mGy. There was a significant increase in the proportion of S phase cells in MSCs in response to 75 mGy X-rays. Activation of several members in the MAPK/ERK signaling pathway, including c-Raf, MEK and ERK were observed in the cells exposed to 75 mGy X-rays. To define the role of ERK activation in LDIR-stimulated cell proliferation, LDIR-treated MSCs were pre-incubated with MEK specific inhibitor U0126, which completely abolished LDIR-increased phosphorylation of ERK and cell proliferation. These results suggest that LDIR stimulates MSC proliferations in the in vitro condition via the activation of MAPK/ERK pathway.
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Meeting Report
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