| Project/Area Number |
15201013
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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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 | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
NORIMURA Toshiyuki Univ.Occup.& Environm.Health, Sch.Med., Professor, 医学部, 教授 (20039530)
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| Co-Investigator(Kenkyū-buntansha) |
OOTSUYAMA Akira Univ.Occup.& Environm.Health, Sch.Med., Associate Professor, 医学部, 助教授 (10194218)
KATO Fumio Univ.Occup. & Environm.Health, Sch.Med., Assistant Professor, 医学部, 講師 (20309959)
FUJIKAWA Kazuo Kinki Univ., Faculty of Science & Technology, Professor, 理工学部, 教授 (90247958)
KUNUGITA Naoki Univ.Occup. & Environm.Health, Sch.Health Science, Associate Professor, 産業保健学部, 助教授 (90178020)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥28,210,000 (Direct Cost: ¥21,700,000、Indirect Cost: ¥6,510,000)
Fiscal Year 2005: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
Fiscal Year 2004: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Fiscal Year 2003: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
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| Keywords | p53 gene / mutation / p53-dependent apoptosis / tissue repair / radiation / dose-rate dependence / genomic instability |
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| Research Abstract |
The major risks of low-dose radiation are mutagenesis, teratogenesis and carcinogenesis. All three have been shown (experimentally) to approach zero risk with decreasing dose rate, demonstrating the critical contribution of DNA repair at low dose-rate irradiation. However, DNA repair is not perfect. There must be defense mechanisms other than DNA repair. The influence of p53 on the radiation-induce elevation of T-cell receptor (TCR) variant fractions was examined in splenic T lymphocytes of p53-proficient and -deficient mice.
(1)After acute gamma-irradiation with 3 Gy (@ 61 Gy/h), the TCR variant fraction was higher than the control level. However, when an equal dose of 3 Gy was given but at a lower dose-rate of 0.07 Gy/h, the fraction of TCR variants did not increase at all for p53(+/+) mice, whereas the same dose of 3 Gy remained mutagenic for p53(-/-) mice, which are unable to carry out p53-dependent apoptosis.
(2)Initially, the TCR variant fraction increased rapidly and reached its maximum level at 9 days after irradiation before decreasing gradually. In p53(+/+) and p53(+/-) mice, the TCR variant fraction fell to normal background levels at 16 and 20 weeks of age, respectively. After the long flat period, a significant re-increase in the fraction of TCR variants was found after 72 weeks of age in the irradiated p53(+/+) mice and after 44 weeks of age in the irradiated p53(+/-) mice. This delayed increase in TCR variants after irradiation is due to a reduction in p53-dependent apoptosis.
These results indicate that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rate.
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