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Volume 49, Issue 1
Displaying 1-10 of 10 articles from this issue
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Award Article
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Tetsuo NAKAJIMA2008 Volume 49 Issue 1 Pages 1-8
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: August 31, 2007JOURNAL FREE ACCESSIndicators such as clonogenic survival, transformation, and chromosomal aberrations are used to evaluate the effects of radiation on cells. Apoptosis, another such indicator, is a mode of cell death, and radiation-induced apoptosis contributes to eliminating damaged cells and preventing malformation and carcinogenesis. Understanding radiation-induced apoptosis will assist in radiotherapy for cancer and treatment of patients in accidental radiation exposure. Protein kinase C (PKC) is a serine/threonine kinase that is related to cell proliferation, differentiation, metabolism, and apoptosis, and has many roles in the radiation-induced cellular responses involving apoptosis. This review describes the functions of PKC, including its relationship with other signaling networks and oxidative stress in the regulation of radiation-induced apoptosis. Such information might provide clues for evaluating the effects of radiation and for identifying clinical applications.View full abstractDownload PDF (205K) -
Hideaki NAKAMURA2008 Volume 49 Issue 1 Pages 9-15
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: December 27, 2007JOURNAL FREE ACCESSTo establish immortal human cells, we introduced the cDNA of the human telomere reverse transcriptase (hTERT) gene into skin fibroblast cells obtained from normal and ataxia telangiectasia (AT) individuals of Japanese origin. hTERT-immortalized cells retained their original characteristics and radiosensitivity except for immortalization, suggesting that these cells might be useful for analyzing the effects of radiation on human cells.
hTERT-immortalized cells from a normal individual showed a greater resistance after low-dose-rate irradiation than after high-dose-rate irradiation. In contrast, cells from AT patients irradiated at a low-dose rate showed virtually the same survival as those irradiated at a high-dose rate. In hTERT-immortalized normal cells, the genetic effects of low-dose-rate radiation were quantitatively and qualitatively less severe than those of high-dose-rate radiation. In hTERT-immortalized AT cells, some fraction of DNA damage such as DNA double-strand breaks might not be repaired, and AT cells were severely affected by low-dose-rate radiation. The activation of ataxia telangiectasia mutated (ATM) protein was confirmed during low-dose-rate radiation, and may play an important role in repair of DNA damage induced by low-dose-rate radiation. This paper reviews briefly the current research at our laboratory. The hTERT-immortalized cells may be useful in determining the effects of low-dose and low-dose-rate radiation on human cells.View full abstractDownload PDF (292K)
Regular Papers
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Michiko MATSUSE, Vladimir SAENKO, Ilya SEDLIAROU, Tatiana ROGOUNOVITCH ...2008 Volume 49 Issue 1 Pages 17-27
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: October 25, 2007JOURNAL FREE ACCESSThyroid hormone receptors (THRs) widely govern cell growth, differentiation and metabolism acting in a ligand- and cofactor-dependent manner to modulate tissue-specific gene expression. Given a large variety of genes regulated by THRs and multiplicity of cellular processes potentially influenced by THRs, we addressed the role of THRB (thyroid hormone receptor beta) in cellular radiosensitivity. Wild-type and mutant THRB were overexpressed in several cell lines using an adenovirus-mediated gene delivery and their effects were examined after cell exposure to γ-rays. Wild-type THRB decreased clonogenic survival of the cell lines with low levels of endogenous THRB, retarded their growth and synergized with radiation in decreasing proliferative potential and promoting cellular senescence. These changes were accompanied by the accumulation of p21 (CDKN1A, CIP1, WAF1) and p16 (CDKN2A, INK4a) inhibitors of cyclin-dependent kinases and by the decrease of Rb (retinoblastoma protein) phosphorylation. Mutant THRB produced a radioprotective effect, attenuated radiation-induced growth inhibition and cellular senescence. The results suggest that THRB may modulate cellular radiosensitivity and stress-induced senescence.View full abstractDownload PDF (883K) -
Mehryar Habibi ROUDKENAR, Li LI, Taisuke BABA, Yoshikazu KUWAHARA, Hir ...2008 Volume 49 Issue 1 Pages 29-40
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: November 30, 2007JOURNAL FREE ACCESSThe liver is one of the target organs of radiation-induced cancers by internal exposures. In order to elucidate radiation-induced liver cancers including Thorotrast, we present a new approach to investigate in vivo effects of internal exposure to α-particles. Adopting boron neutron capture, we separately irradiated Kupffer cells and endothelial cells in mouse liver in vivo and analyzed the changes in gene transcriptions by an oligonucleotide microarray. Differential expression was defined as more than 3-fold for up-regulation and less than 1/3 for under-regulation, compared with non-irradiated controls. Of 6,050 genes examined, 68 showed differential expression compared with non-irradiated mice. Real-time polymerase chain reaction validated the results of the microarray analysis. Exposure to α-particles and γ-rays produced different patterns of altered gene expression. Gene expression profiles revealed that the liver was in an inflammatory state characterized by up-regulation of positive acute phase protein genes, irrespective of the target cells exposed to radiation. In comparison with chemical and biological hepatotoxicants, inductions of Metallothionein 1 and Hemopexin, and suppressions of cytochrome P450s are characteristic of radiation exposure. Anti-inflammatory treatment could be helpful for the prevention and protection of radiation-induced hepatic injury.View full abstractDownload PDF (692K) -
Panagiota MATSOUKA, Panagiotis MYLONAS, Eleni PAPANDONIOU, Irene DIMIT ...2008 Volume 49 Issue 1 Pages 41-47
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: November 30, 2007JOURNAL FREE ACCESSPurpose: Radiation induces apoptosis as a result of damage to cellular DNA and RNA. The aim of our work was to study the effect of radiation on rat bone marrow cells (as a neighboring tissue) in the context of a model of experimental radiation enteritis in rats. The effect of systematic administration in irradiated animals of r-IGF-1 and GH was also studied. Materials and methods: Wistar type, normal rats, were divided in 4 groups. One control group and the other 3 groups were irradiated in the abdomen. The measured scattered irradiation in the femur ranged from 16.5 to 47.3 cGy. In 2 groups of irradiated animals, rIGF-1 (0.1 μg/g of body weight twice/d) and rGH (0.25 μg/g of body weight /d) were administered. Bone marrow cells were harvested from both femurs. DNA and RNA were analyzed in specific gels. The m-RNA was hybridized for c-fos proto-oncogene expression. Results: The calculated low dose of radiation that affected the femurs of the animals induced reduction in bone marrow cell numbers and endonuclease activation manifested by subsequent fragmentation of DNA and RNA. This phenomenon was reversed by rGH and rIGF-1 administration. The c-fos proto-oncogene expression was upregulated by irradiation. Conclusion: These observations indicate that scattered low dose radiation is capable of initiating apoptosis in rat bone marrow cells and rGH and rIGF-1 administration reverse this process.View full abstractDownload PDF (450K) -
Junichi KITAGAWA, Masanori NASU, Hayato OKUMURA, Akihiko SHIBATA, Kimi ...2008 Volume 49 Issue 1 Pages 49-54
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: December 19, 2007JOURNAL FREE ACCESSIt has not been verifiied whether allopurinol application is beneficial in decreasing the severity of radiation-induced oral mucositis and dermatitis. Rats were divided into 4 groups and received 15 Gy irradiation on the left whisker pad. Group 1 received only irradiation. Group 2 was maintained by applying allopurinol/carrageenan-mixed gel (allopurinol gel) continuously from 2 days before to 20 days after irradiation. Group 3 had allopurinol gel applied for 20 days after radiation. Group 4 was maintained by applying carrageenan gel continuously from 2 days before to 20 days after irradiation. The intra oral mucosal and acute skin reactions were assessed daily using mucositis and skin score systems. The escape thresholds for mechanical stimulation to the left whisker pad were measured daily. In addition, the irradiated tissues at the endpoint of this study were compared with naïve tissue. Escape threshold in group 2 was significantly higher than that in group 1, and mucositis and skin scores were much improved compared with those of group1. Concerning escape threshold, mucositis and skin scores in group 3 began to improve 10 days after irradiation. Group 4 showed severe symptoms of mucositis and dermatitis to the same extent as that observed in group 1. In the histophathological study, the tissues of group 1 showed severe inflammatory reactions, compared with those of group 2. These results suggest that allopurinol gel application can mitigate inflammation reactions associated with radiation-induced oral mucositis and dermatitis.View full abstractDownload PDF (1180K) -
Hiroshi IGAKI, Keiichi NAKAGAWA, Hiroshi UOZAKI, Masaaki AKAHANE, Yosh ...2008 Volume 49 Issue 1 Pages 55-62
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: October 12, 2007JOURNAL FREE ACCESSGastrointestinal syndrome after high-dose acute radiation whole body exposure is difficult to treat, although it is a well-known complication. In this report, we describe the clinical and pathological features of a patient who died after the criticality accident which occurred in Japan on 30 September 1999. The patient was estimated to have been exposed to 16-25 Gy equivalent of gamma ray, and died of multiple organ failure after acute radiation syndrome, especially gastrointestinal syndrome, on day 82. The stomach and small intestine contained a large amount of blood clots and the gastrointestinal epithelial cells were almost totally depleted at autopsy. In addition, the degree of the mucosal damage was dependent on the segment of the gastrointestinal tract; the mucosa of stomach, ileum and ascending colon was entirely depleted, but the esophagus, descending and sigmoid colon and rectum retained a small portion of the epithelial cells. From the posture of the patient at the time of exposure, the absorbed dose was presumed to be highest in the right-anterior abdomen. This agreed with the pathological differences in the mucosal damage by the position in the abdomen, which depended presumably on the radiation dose. This is the first report documenting the relationship between the absorbed dose and the severity of gastrointestinal damages in vivo.View full abstractDownload PDF (1877K) -
Qiang LIU, Bo JIANG, Li-Ping JIANG, Ying WU, Xiao-Guang WANG, Feng-Lin ...2008 Volume 49 Issue 1 Pages 63-69
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: January 11, 2008JOURNAL FREE ACCESSOn 26 April 1999, three persons were accidentally exposed by high dose 60Co irradiation. They suffered from severe (one case) or moderate (two cases) hemopoietic form of acute radiation sickness (ARS). As part of the comprehensive treatment, strict reverse isolation and granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy were applied. All the patients recovered after an appropriate treatment for 83 days. In our experience, the correct diagnosis and effective treatment at an early stage proved to be helpful to the patients in pulling out from the critical stage of acute radiation sickness. To avoid menstruation by the female patient just in the critical stage, we modified her menstruation cycle by testosterone. In our view, GM-CSF should be given as early as possible with enough dosage for promoting early hematological reconstruction. The experience obtained from the medical management of these patients is valuable for the treatment of such patients in the future.View full abstractDownload PDF (441K)
Technical Report
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Tomoo FUNAYAMA, Seiichi WADA, Yuichiro YOKOTA, Kana FUKAMOTO, Tetsuya ...2008 Volume 49 Issue 1 Pages 71-82
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: December 29, 2007JOURNAL FREE ACCESSResearch concerning cellular responses to low dose irradiation, radiation-induced bystander effects, and the biological track structure of charged particles has recently received particular attention in the field of radiation biology. Target irradiation employing a microbeam represents a useful means of advancing this research by obviating some of the disadvantages associated with the conventional irradiation strategies. The heavy-ion microbeam system at JAEA-Takasaki, which was planned in 1987 and started in the early 1990's, can provide target irradiation of heavy charged particles to biological material at atmospheric pressure using a minimum beam size 5 μm in diameter. A variety of biological material has been irradiated using this microbeam system including cultured mammalian and higher plant cells, isolated fibers of mouse skeletal muscle, silkworm (Bombyx mori) embryos and larvae, Arabidopsis thaliana roots, and the nematode Caenorhabditis elegans. The system can be applied to the investigation of mechanisms within biological organisms not only in the context of radiation biology, but also in the fields of general biology such as physiology, developmental biology and neurobiology, and should help to establish and contribute to the field of "microbeam biology".View full abstractDownload PDF (1178K)
Lecture Note
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Genevieve M. MATANOSKI, James A. TONASCIA, Adolfo CORREA-VILLASE&Ntild ...2008 Volume 49 Issue 1 Pages 83-91
Published: 2008
Released on J-STAGE: February 01, 2008
Advance online publication: August 10, 2007JOURNAL FREE ACCESSThe risks for four cancers, leukemia, lymphopoietic cancers (LHC), lung cancer and mesothelioma, were studied in workers from shipyards involved in nuclear powered ship overhauls. The population represented a sample of all workers based on radiation dose at study termination. The final sample included 28,000 workers with ≥ 5.0 mSv, 10,462 workers with < 5.0 mSv and 33,353 non-nuclear workers. Nuclear workers had lower mortality rates for leukemia and LHC than US white males but higher rates of lung cancer and a significant five-fold excess of mesothelioma. Dose-dependent analyses of risks in the high exposure group indicated that for each cancer the risk increased at exposures above 10.0 mSv. An internal comparison of workers with 50.0 mSv exposures to workers with exposures of 5.0-9.9 mSv indicated relative risks for leukemia of 2.41 (95% CI: 0.5, 23.8), for LHC, 2.94 (95% CI: 1.0,12.0), for lung cancer, 1.26 (95% CI: 0.9, 1.9) and for mesothelioma, 1.61 (95% CI: 0.4, 9.7) for the higher exposure group. Except for LHC, these risks are not significant. However, the increasing risk with increasing exposure for these cancers, some of which are known to be related to radiation, suggests that low-level protracted exposures to gamma rays may be associated with these cancers. Other agents such as asbestos, which are common to shipyard work, may play a role especially in the risk of mesothelioma. Future follow up of the population would identify bounds on radiation risks for this population for comparison with similar risks estimated from other populations.View full abstractDownload PDF (236K)
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