Regulatory Mechanism of Biological Response to Low-dose Radiations and Its Consequences
低剂量辐射生物反应的调节机制及其后果
基本信息
- 批准号:08408021
- 负责人:
- 金额:$ 12.86万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (A)
- 财政年份:1996
- 资助国家:日本
- 起止时间:1996 至 1998
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Eukaryotic organisms respond sensitively to low-level radiations, and become resistant to the induction of mutation and cell killing by subsequent radiations. The response called radioadaptive response is considered to be a reflection of novel life maintenance mechanism and receiving a special concern in the context of radiation effects as well as life science. This study aimed to elucidate the molecular mechanisms and biological significance of the adaptive response. In 1996-1997, we found that the radioadaptive response is mediated by a circuitry signal transduction pathway involving PKC-alpha/p38 MAPK/PLC-delta, which also played a role in the dose recognition, and that the response was p53 dependent. In this year, the studies were further expended toward the elucidation of the molecular mechanism of the acquirement of radioresistance, and following results were obtained. Radiation induces apoptosis in a p53-dependent manner, but prior irradiation with low-dose abrogate the radiation-induced apoptosis, indicating that radioadaptation blocks the death signal from DNA damage. This has been confirmed by studying the fidelity of rejoining of DNA double strand breaks in the in vitro assay system. The nuclear extract obtained from the cells irradiated with low-dose radiation promoted an error-free rejoining. These lines of evidence strongly point to a possibility that the adaptive response plays a role in the reduction of mutation and escaping from the cellular death, which might be a reflection of a driving force in evolution as well as constitute an underlying mechanism of bioregulation of the biological effects of low-level radiations.
真核生物对低水平辐射反应敏感,并对随后的辐射诱导的突变和细胞杀伤产生抗性。辐射适应反应被认为是一种新的生命维持机制的反映,在辐射效应和生命科学的背景下受到特别关注。本研究旨在阐明这种适应性反应的分子机制及其生物学意义。在1996-1997年,我们发现辐射适应性反应是由涉及PKC-alpha/p38 MAPK/PLC-delta的电路信号转导途径介导的,这也在剂量识别中发挥作用,并且该反应依赖于p53。在这一年中,我们进一步研究了辐射抗性获得的分子机制,并获得了以下结果。辐射以p53依赖的方式诱导细胞凋亡,但先前的低剂量辐照消除了辐射诱导的细胞凋亡,表明辐射适应阻断了DNA损伤的死亡信号。这已经通过研究DNA双链断裂在体外分析系统中重新连接的保真度得到证实。从低剂量辐射照射的细胞中获得的核提取物促进了无差错的再连接。这些证据有力地表明,适应性反应可能在减少突变和逃避细胞死亡中发挥作用,这可能是进化驱动力的反映,也可能构成低水平辐射生物效应的生物调节机制。
项目成果
期刊论文数量(41)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Takata, M., Sasaki, M.S.et al.: "Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells." EMBOJournal. 17. 5497-5508 (1998)
Takata, M.、Sasaki, M.S.等人:“DNA 双链断裂修复的同源重组和非同源末端连接途径在维持脊椎动物细胞染色体完整性方面具有重叠的作用。”
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- 影响因子:0
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Ejima, Y.and Sasaki, M.S.: "Mutations of the ATM gene detected in Japanese ataxia-telangiectasia patients : possible preponderance of the two founder mutations 4612del165 and 7883del5." Human Genetics. 102. 403-408 (1998)
Ejima, Y. 和 Sasaki, M.S.:“在日本共济失调毛细血管扩张症患者中检测到的 ATM 基因突变:两个创始人突变 4612del165 和 7883del5 可能占优势。”
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Ohtani-Fujita,N.et al.: "Hypermethylation in the retinoblastoma gene is associated with unilateral,sporadic retinoblastoma." Cancer Genetics and Cytogenetics. 98. 43-49 (1997)
Ohtani-Fujita,N.等人:“视网膜母细胞瘤基因的高甲基化与单侧、散发性视网膜母细胞瘤有关。”
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Tawa, R., et al.: "Effects of X-ray irradiation on genomic DNA methylation levels in mouse tissure." Journal of Radiation Research. 39. 271-278 (1998)
Tawa, R. 等人:“X 射线照射对小鼠组织基因组 DNA 甲基化水平的影响。”
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Kanoe, H., et al.: "Characteristics of genomic breakpoints in TLS-CHOP translocations in liposarcomas suggest the involvement of translin and topoisomerase II in the Process of translocation." Oncogene. 18. 721-729 (1999)
Kanoe, H. 等人:“脂肪肉瘤中 TLS-CHOP 易位的基因组断点特征表明,易位蛋白和拓扑异构酶 II 参与了易位过程。”
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SASAKI Masao其他文献
SASAKI Masao的其他文献
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{{ truncateString('SASAKI Masao', 18)}}的其他基金
Gene regulation of radiation response
辐射反应的基因调控
- 批准号:
06304049 - 财政年份:1994
- 资助金额:
$ 12.86万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Studies on Molecular Mechanisms of Radiation Response
辐射响应的分子机制研究
- 批准号:
05404078 - 财政年份:1993
- 资助金额:
$ 12.86万 - 项目类别:
Grant-in-Aid for General Scientific Research (A)
Development of the characteristic X-ray generator for biological research
开发用于生物研究的特征X射线发生器
- 批准号:
63880023 - 财政年份:1988
- 资助金额:
$ 12.86万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research
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