Project/Area Number |
07670263
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Experimental pathology
|
Research Institution | National Insutitute of Radiological Sciences |
Principal Investigator |
OGIU Toshiaki The 5th Research Group, Supervising Researcher, 第5研究グループ, 総合研究官 (40106183)
|
Co-Investigator(Kenkyū-buntansha) |
WATANABE Fumiaki The 5th Research Group, National Institute, Post Doctoral Fellow, 第5研究グループ, 科学技術特別研究員
NISHIMURA Mayumi The 5th Research Group, Researcher, 第5研究グループ, 研究員 (70218204)
SHIMADA Yoshiya The 5th Research Group, Senior Researcher, 第5研究グループ, 主任研究官 (10201550)
ISHII Hiroko (OHBA Hiroko) The 5th Research Group, Senior Researcher, 第5研究グループ, 主任研究官 (70159672)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
|
Keywords | scid Mice / Immunodeficiency / Radiosensitivity / DNA repair / Radiation carcinogenesis / Susceptibility for tumor development / Thymic lymphoma / DNA-dependent protein kinase / scidマウス / 急性放射線障害 / 急性障害 / LD_<50(30)> / 造血細胞 / 培養線維芽細胞 |
Research Abstract |
Severe combined immunodeficient (scid) mice are known to be radiosensitive due to their heritable defects of repair of double strand breaks induced by ionizing radiation. We studied the effects of scid mutation on the acute as well as late effects of radiation. Acute 50% lethal dose of gamma-rays for scid, Fl and C.B-17 mice was 4.1,6.5 and 7.1 Gy, respectively. When mice were irradiated with same dose, survival period of Fl mice was shorter than that of C.B-17 mice. The bone marrow cells of scid mice were also radiosensitive as compared to those from other 2 strains. Bone marrow cells from Fl mice were slightly but significantly more radiosensitive than that from C.B-17 mice. These results mean that scid hetrozygotes are more resistant to ionizing radiation when compared with scid homozygotes, but more sensitive than wild-type. In late effect studies, groups of scid, Fl and C.B-17 mice were exposed to a single whole body dose of 1-3 Gy of gamma-rays. Results clearly indicated that scid mice were extremely susceptible for induction of thymic lymphomas as compared to other 2 strains. No difference for induction of thymic lymphomas was observed between Fl mice and C.B-17 mice. Ethyl-nitrosourea, a strong lymphomagen, was administered to scid mice. However, incidence of thymic lymphomas were not so high. These results indicate that close relationship between radiosensitivity and susceptibility for radiogenic development of thymic lymphomas was proved, but effect of scid heterozygosity was not demonstrated. Almost all thymic lymphomas of scid mice were CD4/CD8 double positive. In other organs, relationship between radiosensitivity and susceptibility for tumor development was not demonstrated in this system. Further studies are needed to analyze the effects of scid mutation radiation-induced development of solid tumors.
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