2001 Fiscal Year Final Research Report Summary
Studies on characteristics and mechanism of radiation carcinogenesis in radiosensitive strains of mice
| Project/Area Number |
11670233
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | National Institute of Radiological Sciences |
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Principal Investigator |
OGIU Toshiaki National Institute of Radiological Sciences, Low Does Radiation Effects Research Project, Project Leader, 放射線安全研究センター・低線量生体影響プロジェクト, プロジェクトリーダー (40106183)
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| Co-Investigator(Kenkyū-buntansha) |
TSUJI Hideo National Institute of Radiological Sciences, Ditto, Team Leader, 放射線安全研究センター・低線量生体影響プロジェクト, チームリーダー (40163795)
ISHII Hiroko (OHBA Hiroko) National Institute of Radiological Sciences, Ditto, Senior Researcher, 放射線安全研究センター・低線量生体影響プロジェクト, 主任研究員 (70159672)
SHIMADA Yoshiya National Institute of Radiological Sciences, Ditto, Sub-Project Leader, 放射線安全研究センター・低線量生体影響プロジェクト, サブプロジェクトリーダー (10201550)
NISHIMURA Mayumi National Institute of Radiological Sciences, Ditto, Senior Researcher, 放射線安全研究センター・低線量生体影響プロジェクト, 主任研究員
UKAI Hideki National Institute of Radiological Sciences, Ditto, National Institute Post Doctoral Fellow, 放射線安全研究センター・低線量生体影響プロジェクト, (研究協力者)科学技術特別研究員
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| Project Period (FY) |
1999 – 2001
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| Keywords | Radiation carcinogenesis / C.B-17 Scid mice / DNA repair / DNA-PKcs / C.B-17 mice / Thymic lymphoma / Nochi1 / Mutation |
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| Research Abstract |
The C.B-17 Scid mouse demonstrates immunodeficiency and also radio sensitivity similar to human ataxia-telangiectasia because of mutation in the DNA-PKcs gene. This strain of mice was also susceptible to radiation induction of thymic lymphomas. Therefore, characteristics of radiation carcinogenesis and molecular mechanisms were examined in this study. Scid, C.B-17 and their hybrid F1 mice were irradiated with gamma-rays and spectrum of carcinogenesis was first examined. Scid mice were extremely susceptible to the induction of thymic lymphomas by ionizing radiation, but not C.B-17 and F1 mice. Then irradiated Scid mice were transplanted with normal bone marrow cells of C.B-17 mice just after gamma-ray-irradiation to suppress induction of thymic lymphomas and thereby to examine carcinogenesis in various organs other than the thymus. This treatment completely reduced development of thymic lymphomas, but no excess of other tumors was demonstrated comparing with that in C.B-17 and F1 mice. Next, Scid mice with C3H background (C3H Scid mice) were used to examine effects of genetic background on radiosensitivity and radiation carcinogenesis. C3H Scid were demonstrated to be more radiosensitive and more susceptible to radiation induction of thymic lymphomas compared with C.B-17 Scid mice. Furthermore, presence of modifier gene was suspected Mutations of various cancer-related genes were examined with thymic lymphomas, and mutation of the Notch1 gene encoding cell surface receptor was frequently observed. Length of this gene is 45.6 kb with 34 exons. Although Genomic rearrangement was observed in about 20% of thymic lymphomas of STS and C.B-17 mice, that was more frequent in C.B-17 Scid mice. Detected rearrangements are deletion, IAP insertion and inversion. Furthermore, abnormal mRNA and protein were demonstrated in the tumors. Then, it is suggested that Notch1 gene is an oncogene, which is continuously active and may have a important role in thymic lymphomagenesis.
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Research Products
(15 results)
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[Journal Article] Spectrum of Znfn1a1 (Ikaros) inactivation and its association with loss of heterozygosity in radiogenic T-cell lymphomas in susceptible B6C3F1 mice.2002
Author(s)
Kakinuma, S., Nishimura, M., Sasanuma, S., Mita, K., Suzuki, G., Katsura, Y., Sado, T., Shimada, Y.
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Journal Title
Radiat.Res. 157
Pages: 331-340
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Single nucleotide instability without microsatellite instability in rat mammary carcinomas.2001
Author(s)
Watanabe, N., Okochi, E., Y.Shimada, Y., Yanagihara, K., Yoshida, M., Takahashi, S., Mochizuki, M., Sugimura, T., Nagao, M., Ushijima, T
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Journal Title
Cancer Res. 61
Pages: 2632-2640
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Characteristic association of K-ras gene mutation with loss of heterozygosity in X-ray-induced thymic lymphomas of B6C3F1 mice.2001
Author(s)
Shimada, Y., Nishimura, M., Kakinuma, S., Ogiu, T., Suzuki, G., Nakata, Y., Sasanuma, S., Mita, K., Sado, T.
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Journal Title
Int.J.Radiat.Biol. 77
Pages: 465-473
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Reduced sensitivity to and ras mutation spectrum of N-ethyl-N-nitrosourea-induced thymic lymphomas in adult C.B-17 Scid mice.2001
Author(s)
Nishimura, M., Kakinuma, S., Wakana, S., Mita, K., Sado, T., Ogiu, T., Shimada, Y.
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Journal Title
Mutat.Res. 486
Pages: 275-283
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Absence of linkage between radio sensitivity and the predisposing Atp7b gene mutation for heritable hepatitis in the LEC rat.2000
Author(s)
Ogiu, T., Nishimura, M., Watanabe, F., Ukai, H., Ishii-Ohba, H., Shimada, Y., Tsuji, H., Sakurai, J., Hino, O.
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Journal Title
Radiat.Res. 154
Pages: 113-116
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Radiation-associated loss of heterozygosity at the Znfn1a1 (Ikaros) locus on chromosome 11 in murine thymic lymphomas.2000
Author(s)
Shimada, Y., Nishimura, M., Kakinuma, S., Okumoto, M., Shiroishi, T., Clifton, K.H., Wakana, S.
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Journal Title
Radiat.Res. 154
Pages: 293-300
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Low frequency of ras gene mutation in spontaneous and gamma-ray-induced thymic lymphomas of Scid mice.1999
Author(s)
Nishimura, M., Wakana, S., Kakinuma, S., Mita, K., Ishii, H., Kobayashi, S., Ogiu, T., Sado, T., Shimada, Y.
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Journal Title
Radiat.Res. 151
Pages: 142-149
Description
「研究成果報告書概要(欧文)」より
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