Radiation-induced apoptosis in DNA-double strand break repair deficient cells and its relation to radiation-induced fibrosis
| Project/Area Number |
09670925
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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 |
Radiation science
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
KIMURA Hiroshi Shiga University of Medical Science, School of Medicine, Full Professor, 医学部, 教授 (00110560)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Fibrosis / X-ray effect / Apoptosis induction / p53 tumor suppressor / double strand breaks / DNA-dependent protein kinase / 抗がん剤、SN-38 |
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| Research Abstract |
Apoptosis induction by X-irradiation was investigated in scid (severely combined immunodeficient) cells, cells defective in catalytic subunit of DNA-dependent protein kinase (DNA-PK) and hence deficient in repair of DNA double strand breaks. We established fibroblastic cells from an embryo with homozygous scid genotype by means of 3T3 protocol. Balb/c3T3 cells were used as a control with normal repair. As expected, radiation sensitivity of scid cells was about twice as much as that of Balb/c3T3 cells, when DィイD20ィエD2 values were calculated from each dose-survival curve and were compared. On the other hand, there was seven-time difference between sensitivities of these cells to apoptosis. These facts suggested that DNA -PK is implicated not only in repair of double strand breaks but also in the process of apoptosis induction. To support this, the sensitivity to apoptosis in scid cells was higher than that in Balb/c3T3 cells, when agents that cause various types of DNA lesions but strand breakage were used. It has been reported that apoptosis produced in epithelial cells in tissues seems to lead to sporadic fibrosis. Epithelial cells in tissues may be replaced with fibroblastic cells after removal of these epithelial cells with apoptosis. We planned to investigate whether or not scid mouse is more sensitive to fibrosis than Balb/c mouse. Severe ulcerative inflammation and scar formation were observed in irradiated scid mouse skin. Pathological characterization is now under study.
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Report
(4 results)
Research Products
(21 results)
