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：
7661576
负责人：
Susan M. Bailey
金额：
$ 36.92万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-08-01 至 2013-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7661576
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）：染色体畸变是由于暴露于电离辐射（IR）而引起的许多不良生物效应的根本原因。这些包括导致细胞和生物体死亡的急性效应，以及辐射后数年出现的延迟效应，主要是癌症。当前的技术（例如，全染色体染色）可以充分检测不同染色体之间发生的大多数大规模染色体事件，例如易位。然而，为了增进我们对辐射损伤基本机制的理解，需要提高较小规模事件检测的灵敏度和分辨率，例如DNA双链断裂（DSB）错误重新连接的互补过程，可能发生在给定染色体的臂内，并导致小的缺失或倒位。通过促进对这些“神秘”染色体变化的贡献的进一步了解，本文提出的研究将为IR诱导的基因组损伤及其生物学后果提供有价值的线索。这种理解最终将有助于指导意外暴露或恐怖袭击后可能的干预策略的设计和时机安排。通过促进对“神秘”染色体内变化（间质缺失和倒位）的贡献的增加检测和理解，这里提出的研究将为电离辐射引起的基因组损伤及其生物学后果提供有价值的线索。这种理解最终将有助于指导意外暴露或恐怖袭击后可能的干预策略的设计和时机安排。