RADIATION INDUCED CHROMOSOME DAMAGE IN VIVO

体内辐射引起的染色体损伤

基本信息

批准号：
3188710
负责人：
Antone L Brooks
金额：
$ 13.26万
依托单位：
BATTELLE PACIFIC NORTHWEST LABORATORIES
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-02-01 至 1992-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3188710
关键词：
X ray cancer risk cellular oncology chromosome disorders epithelium hamsters ionizing radiation linear energy transfer liver cells occupational hazard radiation carcinogenesis radiation genetics radiation hazard radiation related neoplasm /cancer radiation sensitivity radioactive waste relative biological effectiveness

项目摘要

Many accidental and occupational radiation exposures involve both deposition of radioactive material and acute external exposure. This produces a range or unique exposure patterns to radiation with both high and low linear energy transfer (LET). These unique exposure patterns can alter the sensitivity of cells to the induction of cancer and genetic damage and modify carcinogenic and genetic risk. Recent research in vitro has demonstrated that low doses of low LET ionizing radiation reduces the frequency of chromatid aberrations induced by subsequent radiation exposure. It was also demonstrated that radiation in late stages of the cell cycle of transformed cells or of cells from individuals with genetic predisposition to cancer produces a large increase in the frequency of chromatid aberrations above those observed in normal cells. The two hypotheses tested in this proposal are that: 1) Radiation exposure from internally deposited radioactive materials in vivo decreases the sensitivity of chromosomes in normal cells to subsequent x-ray exposure. 2) Abnormal cells, which result from low dose rate irradiation from internally deposited radioactive materials, have increased x-ray sensitivity for the induction of chromatid aberrations. These hypotheses will be tested by measuring the radiation sensitivity of chromosomes in epithelial cells of the Chinese hamster liver. The measure will be made as a function of the stage of the cell cycle, LET of internally deposited radioactive materials, and histological stages of cellular progress from normal to cancer cells. The specific aims of this study address the proposed hypotheses by answering three questions. First, what is the relative biological effectiveness of protracted high and low LET radiation for the induction of chromosome aberrations from internally deposited radioactive materials? Second, what is the influence of internally deposited radioactive material with different LET on the radiation sensitivity of the liver cells to the induction of aberrations? Third, how does the radiation sensitivity of the chromosomes change in cells exposed to internally deposited radioactive materials as the cells progress from normal to hyperplastic nodules and on to a neoplastic state?

许多意外和职业辐射暴露都涉及沉积放射性材料和急性外部暴露。这会产生一个范围或高线性和低线性辐射的独特曝光模式能量转移（LET）。这些独特的曝光模式可以改变细胞对癌症诱导和遗传损害的敏感性以及修改致癌和遗传风险。最近的体外研究表明，低剂量的低剂量使电离辐射降低了由随后的辐射暴露。还证明了辐射转化细胞或细胞的细胞周期的后期阶段具有遗传易感性癌症的个体会大大增加在染色单体畸变的频率以上是正常情况下观察到的细胞。该提案中检验的两个假设是： 1）从内部沉积的放射性材料中暴露于体内降低正常细胞中染色体的敏感性对随后的敏感性 X射线暴露。 2）异常细胞，这是由于低剂量速率照射引起的内部沉积的放射性材料具有提高的X射线灵敏度用于诱导染色单体畸变。这些假设将通过测量中国仓鼠肝的上皮细胞中的染色体。措施将作为细胞周期阶段的函数制作，内部沉积的放射性材料和细胞的组织学阶段从正常到癌细胞的发展。本研究的具体目的通过回答提出的假设来解决三个问题。首先，什么是什么长期和低使辐射诱导染色体的辐射内部沉积放射性材料的畸变？第二，什么是内部沉积的放射性材料的影响让肝细胞对诱导的辐射灵敏度畸变？第三，染色体的辐射灵敏度如何变化暴露于内部沉积放射性材料的细胞细胞从正常的结节发展到肿瘤状态？