Project/Area Number |
11680556
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
環境影響評価(含放射線生物学)
|
Research Institution | Science University of Tokyo |
Principal Investigator |
KOJIMA Shiji Science Univ.of Tokyo, Pharmacentical Sciences, Associate Prof., 薬学部, 助教授 (90119579)
|
Project Period (FY) |
1999 – 2000
|
Project Status |
Completed (Fiscal Year 2000)
|
Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | Radiation hormesis / Glutathione / Sigualling / Colcium Ion / 生体体内抗酸化系 / 放射線抵抗性誘導 / マクロファージ様細胞 / mRNA / 放射線抵抗性 / 生体内坑酸化系 |
Research Abstract |
First, the mechanisms of the elevation of glutathione level induced in macrophage-like RAW 264.7 cells by low doses of γ-rays was examined. Doses between 25 and 100 cGy significantly increased the glutathione level at 4 hr post-irradiation. It was also shown that the elevation of glutathione level in cells irradiated with low doses of γ-rays followed the induction of mRNA coding for γ-GCS, a rate-limiting enzyme of the de novo glutathione synthesis pathway. Based on the inhibitory effects of various inhibitors of protein kinases on the induction of γ-GCS mRNA by low-dose γ-ray, it has been suggested that the tyrosine kinase, calcium channel, and protein kinase C activities play an essential role in the low-dose-radiation-induced elevation of cellular glutathione. Then, involvement of glutathione in the appearance of radioresistance and the enhancement of immune function induced by low-dose radiation was examined. As a result, it has been found that the induction of endogenous glutathione in living cells soon afer low-dose γ-ray irradiation is at least partially responsible for the appearance of radioresistance to a subsequent lethal dose of radiation and of the enhancement of immune function.
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