| Project/Area Number |
09480123
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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 |
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 |
KAMIYA Kenji Hiroshima University, Research Institute for Radiation Biology and Medicine, Professor, 原爆放射能医学研究所, 教授 (60116564)
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| Co-Investigator(Kenkyū-buntansha) |
NIWA Ohtsura Kyoto University, Radiation Biology Center, Professor, 放射能生物研究センター, 教授 (80093293)
SUMII Masaharu Hiroshima University, Research Institute for Radiation Biology and Medicine, Res, 原爆放射能医学研究所, 助手 (60284220)
MIYAGAWA Kiyoshi Hiroshima University, Research Institute for Radiation Biology and Medicine, Pro, 原爆放射能医学研究所, 教授 (40200133)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 1998: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1997: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | Mouse hepatoma / SDF-II / Radiation / VL30 / gene expression / RAD54 / genetic instability / homologus recombination / 放射線誘発肝癌 / 肝癌細胞株 / U3 / CAP / LOH / レトロトランスポゾン |
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| Research Abstract |
Genetic changes of radiation-induced mouse hepatomas was studied by analyzing the expression of mRNA and loss of heterozygosity (LOH). We used primary hepatomas and it's cell lines established in-vitro, and got following three results. 1) We tried to identify genes differntially expressed in primary hepatomas compared to normal liver by using differetial display technique. we found five over-expressed genes such as ATPase inhibitor, ribosomal protein L35. plasminogen activator inhibitors apolipoprotein A-IV.and 3-hydroxy-3-metyylglutaryl coenzyme A (HMG-CoA)synthase, and three under-expressed genes such as UDP glucuronosyltransferase-2.4-hydroxyphenylpyruvate dioxygenase. and phospholipid scramblase in primary hepatomas. 2) In hepatoma cell lines, we found the frequent LOH around the locus of Lci on chromosome 4, where C57BL mouse allele was preferentiafly lost. 3) We identified over-expressed two genes in hepatoma cells grown in soft agar culture. one was retrotransposon VL3O, the oth
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er was newly isolated gene, designated SDF-III which had homology to SDF-II.VL3O was highly expressed in testis, ovary, and adrenal gland. Analysis of the expression of VL3O mRNA in liver revealed that the expression of VL3O mRNA had changed from the weak expression of VL3O subgroup 3 in normal livers to the strong expression of VL3O subgroup 1 in hepatomas during hepato-carcinogenesis. The structure of SDF- III protein indicated that this protein was chaperon protein which located in luminal of endplasmic reticulum, and might play a role for protein assembly.
The involvement of mutations in homologus recombination genes, members of the RAD52 epistasis group, was studied in human cancer. We found missense mutations at functional regions of RAD54 and the absence of the wild-type RAD54 expression resulting from aberrant, splicing in primary cancers. Furthermore, we cloned human RALD54 homologue, designated RAD54B, and found homozygous mutations at highly conserved position of RAD54B in primary lymphoma and colon cancer. These findings suggest that some cancers arise through alterations of the homologus recombination gene function. Less
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