Mathematical Sciences: Chromosome Geometry and Chromosome Aberrations

数学科学：染色体几何和染色体畸变

• 批准号: 9302704
• 负责人: Rainer Sachs
• 金额: $ 18万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-15 至 1997-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9302704&HistoricalAwards=false
• 关键词: Mathematical; Sciences; Chromosome; Geometry; Aberrations

9302704 Sachs The investigator models chromosome aberrations in live mammalian cells, emphasizing implications for large-scale chromosome geometry and for the biology of ionizing radiation damage. The study entails developing computer algorithms, explicitly solving stochastic process models, and collaborating with various experimental groups. Production of chromosome damage (for example, illegitimate recombinations, involving the exchange of fragments between two different chromosomes) after induction of DNA double strand breaks during the interphase part of the cell cycle is analyzed, using probabilistic models for DNA geometry, motion, and reactions at the macromolecular level, in particular polymer models for large-scale chromosome structure and motion. Comparisons of the effects of densely ionizing radiation to those of sparsely ionizing radiation, relevant to chromosome geometry and to biological dosimetry, are made. Statistical questions that arise when very detailed experimental information about specific individual chromosomes is made available by modern fluorescent labeling techniques are answered by extending already developed Monte-Carlo simulations based on previously analyzed biological models. Understanding how ionizing radiation damages chromosomes is important in understanding cancer induction by radiation, understanding how to cope with radiation accidents or waste, and improving tumor radiotherapy. Such understanding requires geometric information about the chromosomes in a live human cell; conversely, information about radiation damage contributes to understanding chromosome geometry, which is of fundamental biological importance. While much effort has been devoted to sequencing the DNA in chromosomes and to modeling local geometry of chromosomes, quantitative geometric models of the larger scales of main interest in analyzing radiation produced chromosome aberrations are just now being developed, by the principal investig ator and others. The project combines standard information on the physics of ionizing radiation with these new biological models of chromosome geometry to analyze how the damage is formed. In particular, preliminary mathematical investigations and a literature search show that, due to geometric effects, densely ionizing radiations, such as alpha particles from radon daughters, make a larger fraction of certain specific kinds of damage (e.g. centric chromosome rings) than other kinds of chromosome damaging agents, including sparsely ionizing radiations such as x-rays. This "signature" of densely ionizing radiations should help in realistic assessments of radiation hazards and will help in understanding chromosome geometry. ***

9302704 Sachs 研究人员模拟活体哺乳动物细胞中的染色体畸变，强调对大规模染色体几何形状和电离辐射损伤生物学的影响。 该研究需要开发计算机算法，明确求解随机过程模型，并与各个实验组合作。 使用大分子水平的 DNA 几何、运动和反应的概率模型，特别是大规模染色体结构和运动的聚合物模型，分析了细胞周期间期部分诱导 DNA 双链断裂后染色体损伤的产生（例如，非法重组，涉及两个不同染色体之间的片段交换）。 对与染色体几何形状和生物剂量测定相关的密集电离辐射与稀疏电离辐射的影响进行了比较。 当通过现代荧光标记技术提供有关特定个体染色体的非常详细的实验信息时出现的统计问题可以通过扩展基于先前分析的生物模型的已经开发的蒙特卡罗模拟来回答。 了解电离辐射如何损害染色体对于了解辐射诱发癌症、了解如何应对辐射事故或废物以及改进肿瘤放射治疗非常重要。 这种理解需要有关活体人类细胞中染色体的几何信息；相反，有关辐射损伤的信息有助于理解染色体几何形状，这具有重要的生物学意义。 虽然我们在染色体 DNA 测序和染色体局部几何建模方面投入了大量精力，但主要研究人员和其他人刚刚开发出用于分析辐射产生的染色体畸变的更大尺度的定量几何模型。 该项目将电离辐射物理学的标准信息与染色体几何的这些新生物模型相结合，以分析损伤是如何形成的。特别是，初步数学研究和文献检索表明，由于几何效应，密集电离辐射（例如来自氡子体的 α 粒子）比其他类型的染色体损伤剂（包括稀疏电离辐射（例如 X 射线））对某些特定类型的损伤（例如中心染色体环）造成更大比例。这种密集电离辐射的“特征”应该有助于对辐射危害进行实际评估，并有助于理解染色体的几何形状。 ***