RADIATION INDUCED GENOMIC INSTABILITY

辐射引起的基因组不稳定

• 批准号: 6346380
• 负责人: William F Morgan
• 金额: $ 4.55万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6346380
• 关键词: animal tissue; biomedical resource; environmental health; genome; human tissue

Cellular progression towards the cancerous state frequently is associated with the loss of genomic integrity, expressing as variable genomic changes i.e. instability. The purpose of this study is to provide insights into the molecular, genetic, cytogenetic and cellular processes that maintain genomic integrity or promote genomic instability in cells surviving exposure to ionizing radiation. Specifically this study investigates directly whether the originating event is located intra-or extranuclearly. Chromosomal instability is studied in hamster-human hybrid cells containing human chromosome 4 using fluorescence in situ hybridisation. The unique capabilities of the microbeam allow for the irradiation of cells with alpha-particles through subcellular compartments. Individual cells were imaged and irradiated with 1, 4, 8 , or 16 alpha particles through the nuclear centroid or through the cytoplasm .Cells were maintained in culture for 20-30 cellular divisions as individual clones. Chromosomally aberrant sub-clones were found for nuclear and cytoplasmic irradiations.It is highly probable that a DNA double strand break is not the most efficient initiator of genomic instability.

细胞向癌状态的进展通常是 与基因组完整性的丧失相关，表达为可变的 基因组变化，即不稳定性。 本研究的目的是 提供分子、遗传、细胞遗传学和细胞 维持基因组完整性或促进基因组 暴露于电离辐射后细胞的不稳定性。 具体来说，这项研究直接调查是否起源 事件位于核内或核外。 染色体不稳定性 在含有人类4号染色体的仓鼠-人类杂交细胞中研究 使用荧光原位杂交。 的独特功能 微束允许用α粒子照射细胞 通过亚细胞间室。 对单个细胞进行成像， 用1、4、8或16个α粒子通过核辐射 在培养物中维持细胞 作为单个克隆进行20-30次细胞分裂。 染色体 发现细胞核和细胞质的异常亚克隆 辐射。这是非常有可能的，DNA双链断裂， 不是基因组不稳定性的最有效的引发剂。