CYTOGENETICS--ALPHA PARTICLE INDUCED CHROMOSOMAL CHANGES

细胞遗传学--α粒子诱导的染色体变化

• 批准号: 6102523
• 负责人: CHARLES R GEARD
• 金额: $ 19.08万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102523
• 关键词: DNA damage; X ray; alpha radiation; cancer risk; chromosomes; clinical research; cytogenetics; fibroblasts; fluorescent in situ hybridization; gene mutation; genetic markers; human data; linear energy transfer; neoplasm /cancer epidemiology; radiobiology; radon; respiratory epithelium

Attribution of the principal ionizing radiation hazard to humans as being due to radon is based on the pervasive nature of the gas and perceived biological efficacy of the responsible high LET alpha particles. While it has long been recognized that radiation of high LET may be more biologically damaging, there is in many instances a decline past an optimally effective LET. Ascertainment of the effectiveness of alpha particles over the range of LET's relevant to radon will allow for greater precision in human risk estimates. This is particularly pertinent for environmental levels of radon where the principal cellular insult is from one and only one radon progeny a-particle. The issues to be addressed relate to the primary overall goals of the program project, namely the provision of information on the effects of single a-particles; to assessments of RBE: LET relations to contribute to quality factor estimates; and to seek a characteristic "fingerprint" for a=-particle exposure. Chromosomal changes have been shown to be associated with cell death, mutation and cancer and their quantitative evaluation is the linch pin of this project and provides links with the other projects of this program project. The effects of exactly one or more a-particles per cell nucleus delivered by microbeam will be compared with the effects of mean (Poisson distributed) numbers of a-particles at the same defined LET in normal human bronchial epithelial cells and fibroblasts. The former constitute the principal cell type at risk from radon progeny a-particle exposure. Chromosomal changes induced by defined high LET a-particles will be compared with X-ray induced changes. Changes will be quantitatively evaluated in normal human bronchial epithelial cells in different stages of the cell cycle, both for all changes and for chromosome specific change using FISH. Inter versus intrachromosomal exchange ratios will be compared for a-particles versus X-rays in a search for a dependent consequence of a- particle radiation. Information gained will be analyzed and incorporated into an integrated modeling of biological data and risk estimation (Project 1) with the intent of providing both a more credible assessment of risk and possible a means of accurately attributing alpha particle (radon) induced change.

电离辐射对人类的主要危害 由于氡是基于气体的普遍性质， 负责高LET α粒子的生物功效。 虽然 长期以来，人们已经认识到，高LET的辐射可能更多， 在生物学上有害的，在许多情况下， 最佳有效LET。 确定alpha的有效性 超过与氡相关的LET范围的粒子将允许更大的 人类风险评估的精确度。 这一点尤其适用于 氡的环境水平的主要细胞的侮辱是从 氡子体A粒子是唯一的 要解决的问题 与计划项目的主要总体目标有关，即 提供关于单个a粒子影响的信息; RBE评估：LET关系有助于质量因素 估计;并寻求一个=粒子的特征“指纹” exposure. 染色体的变化已被证明与细胞 死亡、突变和癌症的关系及其定量评价是研究的林奇 针这个项目，并提供了与其他项目的链接，这 程序项目。 每一个细胞核中一个或多个α粒子的作用 将与平均值（泊松）的影响进行比较 正常人在相同定义的LET下的α粒子数 支气管上皮细胞和成纤维细胞。 前者构成了 氡子体a粒子暴露的主要细胞类型。 由确定的高LET α-颗粒诱导的染色体变化将是 与X射线引起的变化相比。 变化将在数量上 在不同阶段的正常人支气管上皮细胞中进行了评估， 细胞周期，包括所有变化和染色体特异性变化 使用FISH。 将比较染色体间和染色体内交换率 对于a粒子和x射线，在寻找a的依赖结果时， 粒子辐射 将对获得的信息进行分析，并将其纳入综合 生物数据建模和风险评估（项目1）， 提供一个更可靠的风险评估和可能的方法， 准确地归因于α粒子（氡）引起的变化。