| Project/Area Number |
14405040
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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 | 海外学術 |
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| Research Field |
環境影響評価(含放射線生物学)
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KIMURA Akiro Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射線医科学研究所, 教授 (70127645)
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| Co-Investigator(Kenkyū-buntansha) |
HYODO Hideo Hiroshima University, Research Institute for Radiation Biology and Medicine, Assistant Professor, 原爆放射線医科学研究所, 講師 (30253074)
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| Project Period (FY) |
2002 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥10,600,000 (Direct Cost: ¥10,600,000)
Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | myelodysplastic syndrome / MDS / atomic bomb survivor / Semipalatinsk / AML-1 / leukemia / Runt domain / radiation / RAS |
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| Research Abstract |
We reviewed the medical records and smears for 36 cases with leukemia and myelodysplastic syndrome (MDS) in residents of Semipalatinsk near former USSR nuclear test site. Eight cases of them were considered to be exposed to radiation based on the fact that the nuclear tests in air were performed between 1949 and 1963. These cases were studied morphologically and molecular biologically. AML1 transcription factor, which plays an important role in the differentiation of hematopoietic stem cell, was analysed for the point mutation by PCR-SSCP and sequencing. AML1 point mutations at runt domain (exon 5) were found in 2 cases. The R177Q mutation was found in 68 year-old Russian female with MDS, who was exposed to radiation at the age between 14 and 28 in Semipalatinsk city. The other P176R mutation was observed in 36 year-old Kazak male with MDS/AML with eosinophilia, who was exposed at the age of 0 and has lived in Abay. We have recently reported that among Hiroshima A-bomb survivors, AML1 point mutations were frequently detected and localized in N-terminal region (including Runt homology domain) in MDS/AML (RAEB, RAEBt and MDS derived AML). In addition, mutations of RTK-RAS pathway genes, were detected in 38% of these cases. These results suggest that radiation exposure in the nuclear tests induced AML1 mutations in their hematopoietic stem cells and the mutated stem cells then transformed to be MDS cells after gain of some additional genetic changes such as RTK-RAS pathway genes.
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