| Project/Area Number | 05270102 |
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Research Institution | Kyoto University |
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Principal Investigator |
UTSUMI Hiroshi Research Reactor Institute, Kyoto University, Radiation Life Science, Professor, 原子炉実験所, 教授 (20025646)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Kazuo Graduate School of Science, Tohoku University, Professor, 大学院・理学研究科, 教授 (20093536)
NIKAIDO Osamu Faculty of Pharmaceutical Science, Kanazawa University, Division of Radiation Bi, 薬学部, 教授 (60019669)
MATSUKAGE Akio Laboratory of Cell Biology, Aichi Cancer Research Institute, Chief, 生物学部, 部長 (90019571)
KASAI Hiroshi Institute of Industrial Ecology Sciences, University of Occupational and Environ, 産業生態科学研究所, 教授 (40152615)
ISHIZAKI Kanji Laboratory of Experimental Radiology, Aichi Cancer Research Institute, Chief, 放射線部, 部長 (70111987)
宮越 順二 京都大学, 医学部, 講師 (70121572)
八木 孝司 京都大学, 医学部, 助教授 (80182301)
松永 司 金沢大学, 薬学部, 助手 (60192340)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed(Fiscal Year 1996)
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| Budget Amount *help |
¥116,800,000 (Direct Cost : ¥116,800,000)
Fiscal Year 1995 : ¥40,000,000 (Direct Cost : ¥40,000,000)
Fiscal Year 1994 : ¥41,800,000 (Direct Cost : ¥41,800,000)
Fiscal Year 1993 : ¥35,000,000 (Direct Cost : ¥35,000,000)
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| Keywords | caffeine / 8-hydroxyguanine / (6-4) photoproduct / DNA polymerase alpha / PCNA / p53-deficient / hMSH3 / 8-ヒドロキシグアニン(oh8Gua) / p53欠損細胞 / PCNA / PCNAとXPAタンパク質との相互作用 / 8-ヒドロキシングアニン(oh8Gua) / interstrand cross-links / PCNAとXPACタンパク質との相互作用 / 8-ヒドロキシグアニン(oh^8Gua) / XPE-BF |
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| Research Abstract |
Utsumi found that factors induced the potentially lethal damage recovery exist in the conditioned medium and are smaller than MW 1000. He also isolated a radiation-sensitive mutant of V79 Chinese hamster cells, which become radio-resistant in presence of caffeine after X-ray irradiation. He showed that this caffeine induced resistance is specific to cell killing by the interstrand cross-link damages. Ihsizaki revealed that much more number of sister chromatid exchanges and less growth arrest were induced by UV in p53-deficient mouse cells than in p53-proficient cells a though p53-deficient cells were no more sensitive to UV or X-ray than normal cells. Kasai found that repair activity for 8-hydroxyguanine, one of the major oxidative DNA damages, is enhanced by cellular oxidative stress. He also found other types of oxidative DNA damage, 2-hydroxyadenine and glyoxal formations, which suggested new mechanisms of mutations. 2-Hydroxyadenine and appeared to induce AT*GC and CG*TA mutations
… More
by base-pairing with T or C.Matsukage has identified a common regulatory element DRE (DNA replication-related element) and a specific transcription factor DREF (DRE-binding factor) which regulate the transcription of a number of Drosophila DNA replication factors such as DNA polymerase alpha and PCNA.The DREF cDNA and gene have been cloned. Furthermore, he found that the ectopic expression of DREF in the eye imaginal disc of transgenice flies repressed differentiation and induce unusual DNA replication. indicating the central role of DREF in cell growth regulation. Nikaido have purified a UV-damaged DNA-binding protein from HeLa cells to homogeneity. They found that it was identical to glyceraldehyde-3-phosphate dehydrogenase, based on the partial amino acid sequence analysis as well as immunological and biochemical analyzes. Miyakoshi reported that human osteosarcoma cells, which have a deletion in p53 gene, become sensitive to ionizing radiation after introduction of wild-type p53. Yamamoto demonstrated that active oxygen species induced (an) as yet identified lesion (s) which leaded to GC*CG tran sversion. Mitani found that (6-4) photolyase could be induced by UVA,blue light, hydrogen peroxide, and growth inhibition by transcriptional regulation or post-transcriptional regulation like photolyase for cyclobutane pyrimidine dimers. Kohno showed that the Dxpa protein was strongly expressed in the central nervous system and muscles as revealed by immunohistochemical analysis using anti-Dxpa antibodies. Ikejima found that expression of the hMSH3 gene, one of the human MutS homologues, significantly decresed in some patients with hematological malignancies and suggested that inactivation of the hMSH3 gene may be involved in leukemogenesis. Genomic structure of the hMSH3 gene was elucidated and it became possible to study the involvement of specific mutations of the gene in some diseases. Fujiwara characterized the group D of Xeroderma pigmentosum. Uchida isolated Droso Less
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