2005 Fiscal Year Final Research Report Summary
Analysis of biological significance of elevated mutation
| Project/Area Number |
15310031
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Risk sciences of radiation/Chemicals
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| Research Institution | Tohoku University |
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Principal Investigator |
ONO Tetsuya Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (00107509)
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| Co-Investigator(Kenkyū-buntansha) |
IKEHATA Hironobu Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (90250737)
UEHARA Yoshihiko Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (30223499)
NAKAMURA Nori Radiation Effects Research Foundation, Department of Genetics, Chief Scientist, 遺伝学部, 部長 (00010116)
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| Project Period (FY) |
2003 – 2005
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| Keywords | mismatch repair / mutation / biological significance / mouse / lacZ |
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| Research Abstract |
Although alterations of genome are supposed to be one of the major causes of cancer and senescence, the details of the process are not know yet. The knock-out mice in the mismatch repair genes showed an elevation of spontaneous mutation and a high incidence of cancer, suggesting a close relationship between genomic alteration and cancer induction. The mice, however, revealed high levels of mutation in many tissues and most of the tissues did not show cancer nor accelerated senescence phenotype. In an attempt to understand a relationship between mutation and cancer or senescence, we analyzed the details of the mutation and tissue alteration in the mismatch repair deficient mice. Both Mlh1 and Msh2-deficient mice showed high levels of mutation in embryo stage, but no appreciable alteration was found in tissue morphology, development or growth. The level of apoptosis was not affected either. We also examined if the cells suffering from radiation-induced chromosomal abnormality could be eliminated from body. The analysis using wild-type mice showed that the frequencies of chromosome abnormality in lymphocytes analyzed 2 to 4 months after irradiation were low when the irradiation was done during late embryo and early neonatal stages but high when irradiated at later age. It suggests a presence of cell elimination system against cells harboring chromosomal abnormality. These studies suggest that the relationship between the elevation of genomic alteration and cancer or senescence is not simple but many biological factors must be intervening between them.
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