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Volume 49 (2008)
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Volume 49, Issue 3
Displaying 1-14 of 14 articles from this issue
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Review
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Megumi HADA, Alexandros G. GEORGAKILAS2008 Volume 49 Issue 3 Pages 203-210
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: April 15, 2008JOURNAL FREE ACCESSRadiation can cause as well as cure cancer. The risk of developing radiation-induced cancer has traditionally been estimated from cancer incidence among survivors of the atomic bombs in Hiroshima and Nagasaki.1) These data provide the best estimate of human cancer risk over the dose range for low linear energy transfer (LET) radiations, such as X- or γ-rays. The situation of estimating the real biological effects becomes even more difficult in the case of high LET particles encountered in space or as the result of domestic exposure to α-particles from radon gas emitters or other radioactive emitters like uranium-238.
Complex DNA damage, i.e., the signature of high-LET radiations comprises of closely spaced DNA lesions forming a cluster of DNA damage. The two basic groups of complex DNA damage are double strand breaks (DSBs) and non-DSB oxidative clustered DNA lesions (OCDL). Theoretical analysis and experimental evidence suggest an increased complexity and severity of complex DNA damage with increasing LET (linear energy transfer) and a high mutagenic or carcinogenic potential. Data available on the formation of clustered DNA damage (DSBs and OCDL) by high-LET radiations are often controversial suggesting a variable response to dose and type of radiation. The chemical nature and cellular repair mechanisms of complex DNA damage have been much less characterized than those of isolated DNA lesions like an oxidized base or a single strand break especially in the case of high-LET radiation. This review will focus on the induction of clustered DNA damage by high-LET radiations presenting the earlier and recent relative data.View full abstractDownload PDF (458K)
Regular Papers
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Sumino YANASE, Naoaki ISHII2008 Volume 49 Issue 3 Pages 211-218
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 16, 2008JOURNAL FREE ACCESSThe hormetic effect, which extends the lifespan by various stressors, has been confirmed in Caenorhabditis elegans (C. elegans). We have previously reported that oxidative stress resistance in a long-lived mutant age-1 is associated with the hormesis. In the age-1 allele, which activates an insulin/insulin-like growth factor-1 (Ins/IGF-1) signaling pathway, the superoxide dismutase (SOD) and catalase activities increased during normal aging. We now demonstrate changes in the mitochondrial superoxide radical (·O2-) levels of the hormetic conditioned age-related strains. The ·O2- levels in age-1 strain significantly decreased after intermittent hyperoxia exposure. On the other hand, this phenomenon was not observed in a daf-16 null mutant. This hormesis-dependent reduction of the ·O2- levels was observed even if the mitochondrial Mn-SOD was experimentally reduced. Therefore, it is indicated that the hormesis is mediated by events that suppress the mitochondrial ·O2- production. Moreover, some SOD gene expressions in the hormetic conditioned age-1 mutant were induced over steady state mRNA levels. These data suggest that oxidative stress-inducible hormesis is associated with a reduction of the mitochondrial ·O2- production by activation of the antioxidant system via the Ins/IGF-1 signaling pathway.View full abstractDownload PDF (566K) -
Hongyu JIANG, Wei LI, Xiuyi LI, Lu CAI, Guanjun WANG2008 Volume 49 Issue 3 Pages 219-230
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 22, 2008JOURNAL FREE ACCESSBiological effects of low-dose radiation (LDR) are distinguishable from those of high-dose radiation. Hormetic and adaptive responses are such two examples. However, whether adaptive response could be induced in tumor cells by LDR, especially under in vivo condition, remains elusive, and was systemically investigated in the present study. Four tumor cell lines: two human leukemia cell lines (erythroleukemia cell line K562, and acute promyelocytic leukemia cell line HL60), and two human solid tumor cell lines (lung carcinoma cell line NCI-H446 and glioma cell line U251), along with one normal cell line (human fibroblast cells, MRC-5), were irradiated with LDR at 75 mGy of X-rays as D1 and then 4 Gy of X-rays as D2 (i.e.: D1 + D2) or only 4 Gy of X-rays (D2 alone). Three tumor-bearing animal models were also used to further define whether LDR induces adaptive response in tumor cells in vivo. Adaptive response was observed only in normal cell line, but not in four tumor cell lines, in response to LDR, showing a resistance to subsequent D2-induced cell growth inhibition. Three tumor-bearing mouse models with U251, NCI-H446 or S180 tumor cells were used to confirm that pre-exposure of tumor-bearing mice to D1 did not induce the resistance of tumor cells in vivo to D2-induced tumor growth inhibition. Furthermore, a higher apoptotic effect, along with higher expression of apoptosis-related genes P53 and Bax and lower expression of anti-apoptosis gene Bcl-2, was found in tumor cells of the tumor-bearing mice exposed to D1 + D2 than those in the tumor cells of the tumor-bearing mice exposed to D2 alone. These results suggest that LDR does not induce adaptive response in the tumor cells under both in vitro and in vivo conditions, which is a very important, clinic-relevant phenomenon.View full abstractDownload PDF (1639K) -
Takashi SUGIHARA, Hayato MURANO, Kimio TANAKA, Yoichi OGHISO2008 Volume 49 Issue 3 Pages 231-240
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 16, 2008JOURNAL FREE ACCESSBased on the results of previous microarray analyses of murine NIH3T3/PG13Luc cells irradiated with continuous low-dose-rate (LDR) γ-ray or end-high-dose-rate-irradiations (end-HDR) at the end of the LDR-irradiation period, the inverse dose-rate-effects on gene expression levels were observed. To compare differences of the effects between LDR-irradiation and HDR-irradiation, HDR-irradiations at 2 different times, one (ini-HDR) at the same time at the start of LDR-irradiation and the other (end-HDR), were performed. The up-regulated genes were classified into two types, in which one was up-regulated in LDR-, ini-HDR-, and end-HDR irradiation such as Cdkn1a and Ccng1, which were reported as p53-dependent genes, and the other was up-regulated in LDR- and ini-HDR irradiations such as pro-collagen TypeIa2/Col1a2, TenascinC/Tnc, and Fibulin5/Fbln5, which were reported as extra-cellular matrix-related (ECM) genes. The time dependent gene expression patterns in LDR-irradiation were also classified into two types, in which one was an early response such as in Cdkn1a and Ccng1 and the other was a delayed response such as the ECM genes which have no linearity to total dose. The protein expression pattern of Cdkn1a increased dose dependently in LDR- and end-HDR-irradiations, but those of p53Ser15/18 and MDM2 in LDR-irradiations were different from end-HDR-irradiations. Furthermore, the gene expression levels of the ECM genes in embryonic fibroblasts from p53-deficient mice were not increased by LDR- and end-HDR-irradiation, so the delayed expressions of the ECM genes seem to be regulated by p53. Consequently, the inverse dose-rate-effects on the expression levels of the ECM genes in LDR- and end-HDR-irradiations may be explained from different time responses by p53 status.View full abstractDownload PDF (914K) -
Natasa TODOROVIC, Istvan BIKIT, Dusan MRDJA, Jaroslav SLIVKA, Sofija F ...2008 Volume 49 Issue 3 Pages 241-248
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 27, 2008JOURNAL FREE ACCESSSediment samples from the Tisza River in Serbia were investigated for possible TENORM pollutants. The radionuclide content of the samples was determined by means of low-level high-resolution gamma-spectroscopy. In addition to the members of the natural radioactive chains of 238U and 232Th and the natural 40K, Chernobyl origin 137Cs was detected in 26 of the 28 samples tested. The higher concentration of 238U in four locations along the river could be caused by extensive exploitation of phosphate fertilizers in the surrounding agricultural area (TENORM). Also, in one location the lowest 40K and the highest 232Th concentration in all samples were detected. Every unexpected distribution is an indication of radioactive contamination.View full abstractDownload PDF (1440K) -
Ryohei YAMAMOTO, Miyuki AKIYAMA, Hiroshi IDE, Kazuo YAMAMOTO, Satoshi ...2008 Volume 49 Issue 3 Pages 249-259
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: March 19, 2008JOURNAL FREE ACCESSReactive oxygen species continuously oxidize DNA bases and threaten the genetic integrity. Thymine glycol (TG), one of the representative oxidized products, is repaired mainly by base excision repair (BER). In Escherichia coli, endonuclease III (Nth) and endonuclease VIII (Nei) are known to actively remove TG from DNA, and the homologs are well conserved in various organisms. These are bifunctional glycosylases, also associated with apurinic/apyrimidinic (AP) lyase activity. In the present study, a monofunctional TG-DNA glycosylase activity is shown to be one of the predominant nuclear activities present in some mouse tissues. By combining hypertonic extraction and column chromatography, we successfully separated the novel activity from majority of the bifunctional activities. Since it has been reported that mNTH1 may not be a dominant nuclear activity, the monofunctional glycosylase activity, together with mNEIL1, may be the major TG-DNA glycosylases in the mouse nucleus. The optimal reaction conditions for the monofunctional activity were found to be pH 7-8 and 100-150 mM KCl, and the activity was resistant to 20 mM EDTA. High monofunctional activity was detected in the spleen and stomach, while the level was significantly lower in the liver, suggesting that the contribution of the monofunctional activity is variable among organs.View full abstractDownload PDF (1124K) -
Yong LIU, Kohsei KUDO, Yoshinao ABE, Masahiko AOKI, Dong-Liang HU, Hir ...2008 Volume 49 Issue 3 Pages 261-268
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 22, 2008JOURNAL FREE ACCESSTumor hypoxia and angiogenesis have been studied extensively. However, the relation between normal tissue injury and hypoxia is still unclear. In this study, we investigated the effect of hypoxia on radiation-induced late rectal injury in mice. The rectum of C57BL/6N mice was irradiated locally with a single dose of 25 Gy and the following experiments were performed including hematoxylin-eosin (H. E.) staining, azan staining, real-time PCR, immunohistochemistry and immunofluorescene. Radiation-induced fibrotic changes were observed from 14 days and reached the peak 30 days after irradiation. The expression of transforming growth factor β1 (TGF-β1), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and endothelial cell marker CD31 increased significantly with the formation of fibrosis induced by irradiation compared with unirradiated control. In addition, the maximum expression of TGF-β1, HIF-1α and VEGF was found at 14, 30 and 90 days after irradiation, respectively. The temporal changes of cytokines were consistent with the dynamic change of fibrosis. Our data suggests that late normal tissue injury involved various cytokines including hypoxia-induced angiogenic cytokines. These results may have important implications in the understanding of radiation-induced late normal tissue injury.View full abstractDownload PDF (1103K) -
Eiichiro MORI, Akihisa TAKAHASHI, Kou KITAGAWA, Saki KAKEI, Daiki TSUJ ...2008 Volume 49 Issue 3 Pages 269-277
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 29, 2008JOURNAL FREE ACCESSApoptosis plays an important role in eliminating cells from populations when cells have been exposed to UV irradiation and damaged. Studies of cells in culture have provided some details of the mechanisms involved when stress response genes act after exposure to UV irradiation and other environmental stresses. However, little is known about the responses of intact sections of human skin growing in organ culture to UV irradiation. In the work reported here, it was found that the response of organ-cultured human skin after exposure to UV irradiation is different than the response of cultured cells. At wavelengths below 300 nm, the action spectrum obtained from organ-cultured skin samples showed a lower sensitivity than that observed at 300 nm, indicating that the overlying stratum corneum and upper epidermal cell layers had probably caused a selective absorption of incident UV radiation at some wavelengths. At 3 hours after UV irradiation, p53 was phosphorylated at Ser 15 and Ser 46, and accumulated in the cell nuclei, notably after exposure to 280-320 nm wavelengths. Accumulations of Bax, active Caspase-3 and cleaved PARP were detected in apoptotic cells at 24 hours post-exposure, along with a reduction of Bcl-2 levels, notably after exposure to 300-365 nm light. This difference in apoptotic responses may result from the characteristics of the different irradiation wavelengths used, and from details in the skin's structure. The data obtained in this study using an organ-culture system utilized direct measurements of the biological effects of different wavelengths of UV lights.View full abstractDownload PDF (771K) -
Seyed Mehdi HASHEMI, Bijan HASHEMI-MALAYERI, Gholamreza RAISALI, Parva ...2008 Volume 49 Issue 3 Pages 279-283
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: May 03, 2008JOURNAL FREE ACCESSRadiotherapy represents the most widely spread technique to control and treat cancer. To increase the treatment efficiency, high energy linacs are used. However, applying high energy photon beams leads to a non-negligible dose of neutrons contaminating therapeutic beams. In addition, using conventional linacs necessitates applying wedge filters in some clinical conditions. However, there is not enough information on the effect of these filters on the photoneutrons produced. The aim of this study was to investigate the change of photoneutron dose equivalent due to the use of linac wedge filters. A high energy (18 MV) linear accelerator (Elekta SL 75/25) was studied. Polycarbonate films were used to measure the dose equivalent of photoneutrons. After electrochemical etching of the films, the neutron dose equivalent was calculated using Hp(10) factor, and its variation on the patient plane at 0, 5, 10, 50 and 100 cm from the center of the X-ray beam was determined. By increasing the distance from the center of the X-ray beam towards the periphery, the photoneutron dose equivalent decreased rapidly for the open and wedged fields. Increasing of the field size increased the photoneutron dose equivalent. The use of wedge filter increased the proportion of the neutron dose equivalent. The increase can be accounted for by the selective absorption of the high energy photons by the wedge filter.View full abstractDownload PDF (295K) -
Tetsuya SAKASHITA, Nobuyuki HAMADA, Daisuke D. IKEDA, Michiyo SUZUKI, ...2008 Volume 49 Issue 3 Pages 285-291
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 22, 2008JOURNAL FREE ACCESSLearning impairment following ionizing radiation (IR) exposure is an important potential risk in manned space missions. We previously reported the modulatory effects of IR on salt chemotaxis learning in Caenorhabditis elegans. However, little is known about the effects of IR on the functional relationship in the nervous system. In the present study, we investigated the effects of γ-ray exposure on the relationship between locomotion and salt chemotaxis learning behavior. We found that effects of pre-learning irradiation on locomotion were significantly correlated with the salt chemotaxis learning performance, whereas locomotion was not directly related to chemotaxis to NaCl. On the other hand, locomotion was positively correlated with salt chemotaxis of animals which were irradiated during learning, and the correlation disappeared with increasing doses. These results suggest an indirect relationship between locomotion and salt chemotaxis learning in C. elegans, and that IR inhibits the innate relationship between locomotion and chemotaxis, which is related to salt chemotaxis learning conditioning of C. elegans.View full abstractDownload PDF (550K) -
Hironori YOSHINO, Kenji TAKAHASHI, Satoru MONZEN, Ikuo KASHIWAKURA2008 Volume 49 Issue 3 Pages 293-303
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: March 14, 2008JOURNAL FREE ACCESSDendritic cells (DCs) are a type of antigen-presenting cell which plays an essential role in the immune system. To clarify the influences of ionizing radiation on the differentiation to DCs, we focused on human peripheral blood monocytes and investigated whether X-irradiated monocytes can differentiate into DCs. The non-irradiated monocytes and 5 Gy-irradiated monocytes were induced into immature DCs (iDCs) and mature DCs (mDCs) with appropriate cytokine stimulation, and the induced cells from each monocyte expressed each DC-expressing surface antigen such as CD40, CD86 and HLA-DR. However, the expression levels of CD40 and CD86 on the iDCs derived from the 5 Gy-irradiated monocytes were higher than those of iDCs derived from non-irradiated monocytes. Furthermore, the mDCs derived from 5 Gy-irradiated monocytes had significantly less ability to stimulate allogeneic T cells in comparison to the mDCs derived from non-irradiated monocytes. There were no significant differences in the phagocytotic activity of the iDCs and cytokines detected in the supernatants conditioned by the DCs from the non-irradiated and irradiated monocytes. These results suggest that human monocytes which are exposed to ionizing radiation can thus differentiate into DCs, but there is a tendency that X-irradiation leads to an impairment of the function of DCs.View full abstractDownload PDF (823K) -
Nabil EL-FARAMAWY2008 Volume 49 Issue 3 Pages 305-312
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: March 19, 2008JOURNAL FREE ACCESSElectron paramagnetic resonance (EPR) has been successfully used as a physical technique for gamma radiation dose reconstruction using calcified tissues. To minimize potential discrepancies between EPR readings in future studies, the effects of cavity response factor, tooth position and donor gender on the estimated gamma radiation dose were studied. It was found that the EPR response per sample mass used for assessment of doses in teeth outside of the 70-100 mg range should be corrected by a factor which is a function of the sample mass. In the EPR measurements, the difference in sensitivity of different tooth positions to γ-radiation was taken into consideration. It was determined that among all the pre-molars and molars tooth positions, the relative standard deviation of sensitivity was 6.5%, with the wisdom teeth and the first molars having the highest and lowest sensitivity to γ-radiation, respectively. The current results reveal no effect of the donor gender on the sensitivity to γ-radiation.View full abstractDownload PDF (460K) -
Hae June LEE, Sang Woo BAE, Gou Young KOH, Yun Sil LEE2008 Volume 49 Issue 3 Pages 313-320
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: April 15, 2008JOURNAL FREE ACCESSAngiopoietin-1 (Ang1) is a vasculogenic factor which is signaled through the endothelial and bone marrow cell-specific, Tie2 receptor tyrosine kinase and has potential therapeutic applications for the induction of angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. In this study, we examined whether Ang1 directly exhibits bone marrow protection after ionizing radiation (IR) using an adenoviral vector of COMP-Ang1 (Ad-COMP-Ang1). This is a variant of Ang1 by replacement of the N-terminal portion of Ang1 with short coiled-coil domains of cartilage oligomeric matrix protein-Angiopoietin 1 (COMP-Ang1) which are, long enough for oligomerization but short enough to avoid problems of aggregation and insolubility. A spleen colony assay after 4.5 Gy whole body radiation, indicated that COMP-Ang1 significantly increased the mean colony numbers. Both the decrease in bone marrow cellularity and increased TUNEL (Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling) positive cells produced by radiation in bone marrow were significantly inhibited by COMP-Ang1 transfer. The expression of the ligands of Ang1 and Tie2 receptors were increased by radiation and, the COMP-Ang1 transfer potentiated this protein expression. Pre-treatment of Ang1 could be beneficial in protecting bone marrow from damage by radiation and COMP-Ang1 may be an effective alternative to native Ang1 for therapeutic purposes.View full abstractDownload PDF (1022K)
Short Communication
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Višnja BOGDANOVIĆ, Karmen STANKOV, Ivana IČEVI&#x ...2008 Volume 49 Issue 3 Pages 321-327
Published: 2008
Released on J-STAGE: May 21, 2008
Advance online publication: February 16, 2008JOURNAL FREE ACCESSRadiotherapy-induced toxicity is a major dose-limiting factor in anti-cancer treatment. Ionizing radiation leads to the formation of reactive oxygen and nitrogen species (ROS/RNS) that are associated with radiation-induced cell death. Investigations of biological effects of fullerenol have provided evidence for its ROS/RNS scavenger properties in vitro and radioprotective efficiency in vivo. Therefore we were interested to evaluate its radioprotective properties in vitro in the human erythroleukemia cell line. Pre-treatment of irradiated cells by fullerenol exerted statistically significant effects on cell numbers and the response of antioxidative enzymes to X-ray irradiation-induced oxidative stress in cells. Our study provides evidence that the pre-treatment with fullerenol enhanced the enzymatic activity of superoxide dismutase and glutathione peroxidase in irradiated K562 cells.View full abstractDownload PDF (369K)
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