Chromosomal alterations in basic mechanisms of radiation injury

辐射损伤基本机制中的染色体改变

基本信息

批准号：
7926353
负责人：
Susan M. Bailey
金额：
$ 9.99万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-22 至 2010-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7926353
关键词：
Accidents Acute Biological Biological Markers Biological Models Cancer cell line Cells Cessation of life Charge Chromatids Chromatin Structure Chromosomal translocation Chromosome Deletion Chromosome Painting Chromosome abnormality Chromosome inversion Chromosomes Chromosomes, Human, Pair 10 Color Complement Complex Computer Systems Development Cytogenetics DNA Double Strand Break DNA Sequence Rearrangement Detection Dose Electrons Event Exposure to Frequencies Future Genes Genetic Transcription Genome Goals Hematologic Neoplasms Human Human Chromosomes In Vitro Individual Injury Intervention Ionizing radiation Lead Location Lymphocyte Malignant Neoplasms Malignant neoplasm of thyroid Maps Methodology Mitosis Monitor Organism Paint Population Process Radiation Radiation Injuries Radiation induced double strand break Resolution Risk Survivors Syndrome Technology Testing Time Upper arm biodosimetry carcinogenesis cell type density design genome-wide improved insight interstitial irradiation leukemia particle pressure radiation effect research study response tumor

项目摘要

DESCRIPTION (provided by applicant): Chromosomal aberrations figure prominently as the underlying cause of many untoward biological effects caused by exposure to ionizing radiation (IR). These include acute effects responsible for cell and organism death, as well as delayed effects, principally cancers, that arise years post-irradiation. Current technology (e.g., whole chromosome painting) permits adequate detection of most large-scale chromosomal events that occur between different chromosomes, such as translocations. However, in order to advance our understanding of basic mechanisms of radiation injury, there is a need to improve the sensitivity and resolution of detection of smaller scale events, such as the complementary processes of mis-rejoining of DNA double strand breaks (DSBs) that can occur within an arm of a given chromosome, and which lead to either small deletions or inversions. By facilitating an increased understanding of the contribution of these "cryptic" chromosomal changes, the studies proposed here will provide valuable clues into the processes involved in IR-induced injury to the genome and its biological consequences. Such an understanding will ultimately serve to guide the design and timing of possible intervention strategies following accidental exposure or terrorist attack. By facilitating increased detection and understanding of the contribution of "cryptic" intra-chromosomal changes (interstitial deletions and inversions), the studies proposed here will provide valuable clues into the processes involved in ionizing radiation-induced injury to the genome and its biological consequences. Such an understanding will ultimately serve to guide the design and timing of possible intervention strategies following accidental exposure or terrorist attack.

描述（由申请人提供）：染色体畸变以突出的原因是导致因电离辐射（IR）而引起的许多不良生物学作用的根本原因。其中包括导致细胞和生物体死亡的急性作用，以及延迟作用（主要是癌症），这些癌症是在辐射后出现的。当前的技术（例如，整个染色体绘画）允许对不同染色体（例如易位）之间发生的大多数大型染色体事件进行足够的检测。但是，为了促进我们对辐射损伤的基本机制的理解，需要提高检测较小规模事件的敏感性和分辨率，例如可以在给定的染色体内部发生的DNA双链断裂（DSB）的互补过程，并导致小deletions of the Chormosose。通过促进对这些“神秘”染色体变化的贡献的更多了解，此处提出的研究将为IR诱导的基因组损伤及其生物学后果涉及的过程提供宝贵的线索。这种理解最终将有助于指导意外暴露或恐怖袭击后可能采取的干预策略的设计和时机。通过促进对“神秘”的染色体内变化（间质缺失和反转）的贡献的促进和理解，此处提出的研究将为电离辐射诱导的对基因组及其生物学后果涉及的过程提供有价值的线索。这种理解最终将有助于指导意外暴露或恐怖袭击后可能采取的干预策略的设计和时机。