Responses of human stem cells to ionizing radiation exposures

人类干细胞对电离辐射暴露的反应

• 批准号: 9154067
• 负责人: Ronald Neumann
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9154067
• 关键词: Background Radiation; Cancer cell line; Cell Culture Techniques; Cell Line; Cells; Diagnostic Imaging; Exhibits; Gene Activation; Gene Expression; Genetic; Human Cell Line; Individual; Ionizing radiation; Knowledge; Medicine; Modeling; Molecular; Molecular Genetics; Molecular Profiling; Mutation; Normal Cell; Normal tissue morphology; Pattern; Radiation Tolerance; Stem cells; Testing; Tissues; United States National Institutes of Health; base; cancer radiation therapy; cell type; clinical application; comparative; established cell line; human embryonic stem cell; human stem cells; irradiation; progenitor; research study; response

The majority of our knowledge about the molecular mechanisms of cellular responses to ionizing radiation is based on experiments with traditional cell culture models. For models, cancer cell lines were used the most often, which historically was reasonable given that radiation therapy of cancers is an important clinical application of ionizing radiation in medicine. Now, concerns are being expressed about the consequences of lower exposures, i.e. diagnostic imaging test exposures. It is quite obvious that hESC, primary cell lines, established normal cell lines and cancer cell lines have different responses to IR. The results obtained from experiments using cultures of terminally differentiated cells may not reflect the response to IR of a normal tissue that consists of multiple cell types, including progenitor and tissue stem cells. Because we have access to a number of hESC lines approved for NIH Intramural experiments, I wish to use these genetically distinct hESC to determine by experimentation whether patterns of gene activation following irradiation are truly common across all early human cell lines or whether each line will exhibit, in part because of genetic differences, a distinct response to external and internal irradiations of various types and levels.

我们关于细胞对电离辐射的分子机制的大多数知识是基于传统细胞培养模型的实验。对于模型，最常使用癌细胞系，鉴于癌症的放射治疗是医学中电离辐射的重要临床应用，这在历史上是合理的。现在，人们对较低暴露的后果表示担忧，即诊断成像测试暴露。很明显，hESC，原代细胞系，建立的正常细胞系和癌细胞系对IR的反应不同。从实验中使用末端分化细胞培养的实验获得的结果可能不会反映出由多种细胞类型组成的正常组织的IR反应，包括祖细胞和组织干细胞。 由于我们可以使用批准用于NIH壁内实验的许多hESC线，因此我希望使用这些遗传上不同的hESC来确定辐射后基因激活的模式是否在所有早期的人类细胞系中确实很常见，或者每条线在所有生物细胞系中是否确实会表现出来，部分原因是遗传差异，对外部和各种类型和各种类型和水平的遗传差异的反应。