| DOI: | 10.2172/1128716
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| 报告号: | DOE/CSU--64350
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| 报告题名: | Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation |
| 作者: | Bedford, Joel
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| 出版年: | 2014
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| 发表日期: | 2014-04-18
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| 国家: | 美国
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| 语种: | 英语
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| 英文关键词: | Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation
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| 英文摘要: | Our laboratory has, among other things, developed and used the gamma H2AX focus assay and other chromosomal and cell killing assays to show that differences in this DNA double strand break (dsb) related response can be clearly and distinctly demonstrated for cells which are mildly hyper-radiosensitive such as those associated with A-T heterozygosity. We have found this level of mild hypersensitivity for cells from some 20 to 30 % of apparently normal individuals and from apparently normal parents of Retinoblastoma patients. We found significant differences in gene expression in somatic cells from unaffected parents of Rb patients as compared with normal controls, suggesting that these parents may harbor some as yet unidentified genetic abnormality. In other experiments we sought to determine the extent of differences in normal human cellular reaponses to radiation depending on their irradiation in 2D monolayer vs 3D organized acinar growth conditions. We exmined cell reproductive death, chromosomal aberration induction, and the levels of Îł-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 hours of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose-responses of these cells under the 2D or 3D growth conditions. While this does not mean such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur. In another series of studies in collaboration with Dr Chuan Li, with supprt from this current grant. We reported a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated the proliferation of progenitor or stem cells. In yet another collaboration with Dr, B. Chen with funds from this grant, the relative radiosensitivity to cell killing as well as chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective at phosphorylation sites or kinase activity) were examined after exposure of synchronized G1 cells to 137Cs c rays. DNA-PKcs mutant cells defective in phosphorylation at multiple sites withinthe T2609 cluster or within the PI3K domain displayed extreme radiosensitivity. Cells defective at the S2056 cluster or T2609 single site alone were only mildly radiosensitive, but cells defective at even one site in both the S2056 and T2609 clusters were maximally radiosensitive. Thus a synergism between the capacity for phosphorylation at the S2056 and T2609 clusterswas found to be critical for induction of radiosensitivity. |
| URL: | http://www.osti.gov/scitech/servlets/purl/1128716
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| Citation statistics: |
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| 资源类型: | 研究报告
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/41547
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| Appears in Collections: | 过去全球变化的重建
影响、适应和脆弱性
科学计划与规划
气候变化与战略
全球变化的国际研究计划
气候减缓与适应
气候变化事实与影响
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| 1128716.pdf（8720KB） | 研究报告 | -- | 开放获取 | | View
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| Recommended Citation: | |
Bedford, Joel. Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation. 2014-01-01.
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