Journal of Radiation Research
Online ISSN : 1349-9157
Print ISSN : 0449-3060
Volume 43, Issue 2
Displaying 1-10 of 10 articles from this issue
Regular Papers
  • KATARÍNA KROPÁCOVÁ, LUCIA SLOVINSKÁ, EVA M ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 125-133
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    The transgenerational transmission of radiation damage of rat genom was studied on the basis of cytogenetic changes in somatic cells (hepatocytes). It was found, that the irradiation of rat males with dose of 3 Gy of gamma radiation caused latent cytogenetic damage to the liver, which was expressed during the course of an induced proliferation of hepatocytes (by partial hepatectomy) by lower proliferative activity and a high frequency of chromosomal aberrations. In the progeny of irradiated males (in the F1 generation), the radiation damage to DNA was manifested by similar changes, i.e. by lower proliferation activity and increase in "spontaneus" chromosomal aberration occurence in liver regeneration after partial hepatectomy. Irradiating the progeny of irradiated males (the total radiation load of the progeny being 3 Gy + 3 Gy) caused slighter changes in compared with irradiating the progeny of non-irradiated control males (the total radiation load of the progeny being 0 Gy + 3 Gy), which suggests some kind of adaptive response, which was also found in other experimental systems and parameters. An analogous course of RNA and DNA quantitative changes in the liver of the F0 and F1 generations of rats confirms the partial transmission of radiation damage of genom to the progeny.
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  • KOUICHI YAMAMOTO, NORIAKI TAKEDA, ATSUSHI YAMATODANI
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 135-141
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    We investigated whether radiation-induced pica, a behavior characterized by the eating of a non-food substance, such as kaolin, can be used as an index of radiation-induced vomiting in rats. Since there was an individual difference in the susceptibility to pica, we selected rats that actually ate kaolin following X-ray irradiation, and used them for the experiment. The total-body irradiation (TBI) increased kaolin consumption in a dose-dependent manner (sham, 0.05 ± 0.03 (SEM) g; 2 Gy, 0.38 ± 0.11 g; 4 Gy, 1.54 ± 0.28 g; 8 Gy, 3.55 ± 0.67 g), and the increased kaolin consumption after 4 Gy of TBI was inhibited by a pretreatment with the serotonin 5-HT3 receptor antagonist ondansetron (2 mg/kg, i.p.) (saline, 1.49 ± 0.33 g; ondansetron, 0.75 ± 0.11 g). Furthermore, 4 Gy of abdominal irradiation was more effective to induce pica than that of head irradiation (abdomen: 0.37 ± 0.05 g, head: 0.06 ± 0.01 g). These findings suggested that peripheral serotonergic pathway is predominantly involved in the development of radiation-induced pica in rats and that the radiation-induced pica could be useful as a behavioral index for the severity of radiation-induced vomiting in rats.
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  • SENTARO TAKAHASHI, XUE-ZHI SUN, YOSHIHISA KUBOTA, NOBUHIKO TAKAI, KUMI ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 143-152
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    The left cerebral hemispheres of adult Sprague-Dawley rat brains were irradiated at doses of 30, 50, or 100 Gy with charged carbon particles (290 MeV/nucleon; 5 mm spread-out Bragg peak). The spread-out Bragg peak used here successfully and satisfactorily retained its high-dose localization in the defined region. A histological examination showed that necrotic tissue damage, hemorrhage in the thalamus, and vasodilatations around the necrotic region were induced at 8 weeks after 100 Gy irradiation. The regions with tissue damage correlated well with those expected from the radiation-dose distribution, indicating an advantage of charged carbon particles for irradiating restricted brain regions. An X-ray fluorescent analysis demonstrated a decrease in the concentrations of K and P, and an increase in the concentrations of Cl, Fe, Zn in the damaged region at 8 weeks post-irradiation, though no significant changes were observed before 4 weeks of post-irradiation. This may indicate that even the very high radiation doses used here did not induce acute and immediate neuronal cell death, in contrast with ischemic brain injury where acute neuronal cell death occurred and the elemental concentrations changed within a day after the induction of ischemia.
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  • REMA RAJAGOPALAN, KHALIDA WANI, NAGARAJ G. HUILGOL, TSUTOMU V. KAGIYA, ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 153-159
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    Alpha-tocopherol monoglucoside (TMG), a water-soluble derivative of α-tocopherol, has been examined for its ability to protect DNA against radiation-induced strand breaks. Gamma radiation, up to a dose of 6 Gy (dose rate, 0.7 Gy/ minute), induced a dose-dependent increase in single strand breaks (SSBs) in plasmid pBR322 DNA. TMG inhibited the formation of γ-radiation induced DNA single strand breaks (SSBs) in a concentration-dependent manner; 500 μM of TMG protected the single strand breaks completely. It also protected thymine glycol formation induced by γ-radiation in a dose-dependent manner, based on an estimation of thymine glycol by HPLC.
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  • MIZUHO AOKI, YOSHIYA FURUSAWA, YUTA SHIBAMOTO, ATARU KOBAYASHI, MICHIH ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 161-166
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    We investigated the sensitizing effect of the 2-nitroimidazole analogue doranidazole, a new hypoxic radiosensitizer, on radiation-induced apoptosis in L5178Y cells. Apoptosis was assessed by checking DNA ladder formation, the presence of sub-G1 peaks in flow cytometry, and chromatin condensation. A radiosensitizing effect of doranidazole was also confirmed by a soft-agar colony assay of surviving cells. In the assay of DNA ladder formation, DNA fragmentation was observed following irradiation under an aerobic or hypoxic condition with or without doranidazole. The proportions of the cells at the sub-G1 peak in a flow cytometric measurement was not very different among the irradiations at 5 Gy under the aerobic condition, 15 Gy under hypoxia, and 10 Gy with 1 mM doranidazole under hypoxia. The fraction of cells with chromatin condensation was found to be significantly increased with doranidazole up to 3 mM when applied under hypoxic irradiation, but did not increase even at 10 mM. The sensitizer enhancement ratio was estimated to be about 1.7 with a concentration of 1 mM. This enhancement ratio was not different from that observed by assaying cell survivals. On the other hand, doranidazole showed no radiosensitizing effect under aerobic conditions with 1 mM. In conclusion, the radiation-induced apoptosis of L5178Y cells was enhanced by doranidazole under hypoxia.
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  • HIDEAKI NAKAMURA, HIROKO FUKAMI, YUKO HAYASHI, TOHRU KIYONO, SHIGEKAZU ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 167-174
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    To establish immortal human cells, we introduced the human catalytic subunit of telomerase (hTERT) gene into skin fibroblast cells obtained from normal and ataxia telangiectasia (AT) individuals of Japanese origin. After hTERT introduction, these cells continue to grow beyond a population doubling number of 200 while maintaining their original radiosensitivity. Inductions of p53, phosphorylation of Ser15 in p53, and induction of p21 by X-ray irradiation in immortal cells derived from normal individual were not affected by the hTERT introduction. Both normal and AT immortal cells exhibited an apparent inhibition of growth as original primary cells when they reached confluence. Karyotype analysis has revealed that they are in a diploid range. These results suggest that cells immortalized by hTERT introduction retain their original characteristics except for immortalization, and that they may be useful for analyzing various effects of radiation on human cells.
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  • DOO-PYO HONG, NOBUKO MORI, SEIICHI UMESAKO, CHANG-WOO SONG, YEONG-GWAN ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 175-185
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    Regions of allelic loss on chromosomes in many tumors of human and some experimental animals are generally considered to harbor tumor-suppressor genes involved in tumorigenesis. Allelotype analyses have greatly improved our understanding of the molecular mechanism of radiation lymphomagenesis. Previously, we and others found frequent loss of heterozygosity (LOH) on chromosomes 4, 11, 12, 16 and 19 in radiation-induced lymphomas from several F1 hybrid mice. To examine possible contributions of individual tumor-suppressor genes to tumorigenesis in p53 heterozygous deficiency, we investigated the genome-wide distribution and status of LOH in radiation-induced lymphomas from F1 mice with different p53 status. In this study, we found frequent LOH (more than 20%) on chromosomes 4 and 12 and on chromosomes 11, 12, 16 and 19 in radiation-induced lymphomas from (STS/A X MSM/Ms)F1 mice and (STS/A X MSM/Ms)F 1-p53KO/+ mice, respectively. Low incidences of LOH (10-20%) were also observed on chromosomes 11 in mice with wild-type p53, and chromosomes 1, 2, 9, 17 and X in p53 heterozygous-deficient mice. The frequency of LOH on chromosomes 9 and 11 increased in the (STS/A X MSM/Ms)F1- p53KO/+ mice. Preferential losses of the STS-derived allele on chromosome 9 and wild-type p53 allele on chromosome 11 were also found in the p53 heterozygous-deficient mice. Thus, the putative tumor-suppressor gene regions responsible for lymphomaganesis might considerably differ due to the p53 status.
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  • DOO-PYO HONG, KIHEI KUBO, NAOMI TSUGAWA, NOBUKO MORI, SEIICHI UMESAKO, ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 187-194
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    The loss of heterozygosity (LOH) has been reported in numerous neoplasms in both human and animals, and has often been observed in chromosomal regions, which contain tumor-suppressor genes. We previously found frequent LOH on chromosomes 4, 12 and 19 in radiation-induced lymphomas from (BALB/cHeA x STS/A)F1 hybrid mice by allelotype analysis at polymorphic microsatellite loci. In this study, to elucidate the nature of allelic losses, we refined the loss regions on chromosomes 4, 12 and 19 of the tumors from the F1 mice and then analyzed them cytogenetically. The results represent evidence of a wide range of allelic losses owing to mitotic recombination on chromosomes 4 and 19 in the tumors, possibly reflecting functional losses of putative tumor-suppressor genes. It is suggested that the generation of these large homozygous chromosomal segments probably containing the affected genes is one of the genetic alterations responsible for tumorigenesis.
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  • EIJI YAMAMURA, EUN HYE LEE, AKIHIRO KUZUMAKI, NORIO UEMATSU, TATSUO NU ...
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 195-203
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    To examine the role of the soxRS regulon in mutagenesis, we characterized the spontaneous mutations occurring in the endogenous tonB gene in the ΔsoxR strain and the SoxS overproducing strain of Escherichia coli. Neither the ΔsoxR strain nor the SoxS overproducing strain led to an enhancement or diminishment of the spontaneous mutation frequency. By DNA sequencing, we determined 50 spontaneous mutants from the ΔsoxR strains, and found that 36% were both base substitutions and IS insertions, 14% frameshifts and 10% deletions. Among the base substitutions, G:C→T:A transversions and G:C→A:T transitions predominated, followed by A:T→T:A transversions. We determined 54 spontaneous mutants from the SoxS overproducing strains, and found that 37% were IS insertions, 31% base substitutions, 17% frameshifts, 9% deletions and 6% duplications. Among the base substitutions, G:C→T:A transversions dominated, followed by A:T →T:A transversions and G:C→A:T transitions. These results were similar to those from the soxRS + strains. Thus, it is suggested that the soxRS-regulated genes do not play a significant role in the defense against spontaneous mutagenesis.
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Short Communication
  • KEIKO SUZUKI, MASAHIKO MORI, FUMIHIKO KUGAWA, HIROSHI ISHIHARA
    Article type: Regular papers
    2002 Volume 43 Issue 2 Pages 205-210
    Published: 2002
    Released on J-STAGE: July 19, 2002
    JOURNAL FREE ACCESS
    Activation of the stress-inducible heme oxygenase-1 (HO-1) gene by X-irradiation was investigated in rat liver. When male Wistar MS strain rats (8 weeks) received whole-body irradiation of 17.0 Gy, 7 h later the activity of heme oxygenase in the liver was significantly enhanced (2.5 times). The level of HO-1 mRNA expression was increased by 2.3 and 4.0 times 2 and 4 h after radiation, and then declined at 7 and 10 h to the level of 2.0 and 1.6 times of the control. When the X-ray dose was varied from 4.0 to 21.7 Gy, the transcription of the gene was enhanced at all doses and the level of activation was dose-dependent. Finally, western blotting of irradiated liver demonstrated a significant increase in the level of HO-1 induced by X-rays, peaking at 4 h. Thus, X-rays were confirmed to be stressors that induce acute HO-1 expression transiently in the liver.
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