权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

GENOMIC INSTABILITY IN HIGH LET CARCINOGENESIS

High Let 致癌过程中的基因组不稳定性

基本信息

批准号：
6376383
负责人：
ROBERT L ULLRICH
金额：
$ 11.7万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-09-30 至 2003-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6376383
关键词：
DNA repair animal genetic material tag apoptosis breast neoplasms carcinogen testing gene mutation high energy particle laboratory mouse linear energy transfer mammary epithelium mutagen testing mutagens radiation carcinogen radiation carcinogenesis radiation genetics tissue /cell culture tumor suppressor genes

项目摘要

DESCRIPTION: (Applicant's Description) The objective of this research is to determine the role of radiation-induced genomic instability in radiation carcinogenesis. Previous studies have led the applicant to propose a model identifying genomic instability as the earliest cellular event in the multi-step sequence leading to radiation-induced cancer. To determine whether the induction of instability is mechanistically linked to cancer development requires information be obtained on induction maintenance, and propagation of genomic instability in vivo. Of particular relevance to this application are results demonstrating qualitative differences between effects of high and low LET radiations. If genomic in-stability is critical, it would be predicted that radiation quality should influence its degree and nature. These studies address several issues fundamental to testing the hypothesis and determining effects as a function of radiation quality. Specifically, the aims of this research are: 1) Determine the influence of cell environment on induction, persistence, and propagation of genomic instability as a function of radiation quality. Studies will examine induction of delayed instability by gamma rays, protons, neutrons and iron particles in mouse mammary epithelial cells irradiated in vitro and in vivo. Emphasis will be on the role of cell-cell interactions and cell proliferation. 2) Determine the impact of alterations in "critical" genes involved in cell cycle checkpoint control and apoptosis in radiation-induced instability. Studies will test whether genomic instability after high and low LET irradiation is associated with alterations in cell cycle check point control and the degree to which programmed cell death influences its propagation. 3) Characterize cellular processes involved in the development of radiation-induced instability. To test whether DNA repair mechanisms are involved in induction and propagation of instability, agents which influence repair processes will be used to modify development of instability post-irradiation. The in vivo/in vitro models provide an opportunity for detailed studies of radiation-induced genomic instability to test whether there is a mechanistic link between radiation-induced instability and carcinogenesis and whether there are differences as a function of radiation quality.

描述：（申请人的描述）本研究的目的是确定辐射诱导的辐射致癌作用中的基因组不稳定性先前的研究已经导致申请人提出了一种模型，将基因组不稳定性鉴定为多步骤序列中最早的细胞事件导致辐射诱发的癌症以确定是否诱导不稳定与癌症发展有机械联系，在诱导维持和繁殖中获得基因组不稳定性， vivo. 与本申请特别相关的结果表明，高LET辐射和低LET辐射的影响之间的定性差异。如果基因组不稳定性是至关重要的，可以预测，辐射质量应影响其程度和性质。这些研究涉及检验假设和确定效应的几个基本问题作为辐射质量的函数。具体而言，本研究的目的 1）确定细胞环境对诱导的影响，基因组不稳定性的持续性和传播，辐射质量研究将检查延迟不稳定的诱导， γ射线、质子、中子和铁粒子对小鼠乳腺上皮细胞的影响体外和体内照射的细胞。重点将放在以下方面的作用：细胞-细胞相互作用和细胞增殖。 2)确定影响参与细胞周期检查点控制的“关键”基因的改变以及辐射诱导的不稳定性中的凋亡。研究将测试是否高和低LET照射后的基因组不稳定性与细胞周期检查点控制的改变以及程序性细胞死亡影响其繁殖。 3)表征细胞辐射引起的不稳定性的发展所涉及的过程。到测试DNA修复机制是否参与诱导和繁殖不稳定性，影响修复过程的试剂将用于改变辐照后不稳定性的发展。体内/体外模型提供了一个机会，详细研究辐射引起的基因组的不稳定性，以测试是否有一个机械的联系，辐射引起的不稳定和致癌作用，以及是否有差异作为辐射质量的函数。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Radiation-induced cytogenetic instability in vivo.

辐射诱导的体内细胞遗传学不稳定。

DOI：
发表时间：
1999
期刊：
Radiation research.
影响因子：
0
作者：
Ullrich,RL;Davis,CM
通讯作者：
Davis,CM

Radiation induces genomic instability and mammary ductal dysplasia in Atm heterozygous mice.

辐射会导致 Atm 杂合子小鼠基因组不稳定和乳腺导管发育不良。

DOI：
10.1038/sj.onc.1204589
发表时间：
2001
期刊：
Oncogene.
影响因子：
0
作者：
Weil,MM;Kittrell,FS;Yu,Y;McCarthy,M;Zabriskie,RC;Ullrich,RL
通讯作者：
Ullrich,RL

Elevated breast cancer risk in irradiated BALB/c mice associates with unique functional polymorphism of the Prkdc (DNA-dependent protein kinase catalytic subunit) gene.

DOI：
发表时间：
2001-03
期刊：
Cancer research
影响因子：
11.2
作者：
Yongjia Yu;R. Okayasu;Michael M. Weil;Andy Silver;Maureen McCarthy;Ryan C. Zabriskie;Scott Long;Roger Cox;Robert L. Ullrich
通讯作者：
Yongjia Yu;R. Okayasu;Michael M. Weil;Andy Silver;Maureen McCarthy;Ryan C. Zabriskie;Scott Long;Roger Cox;Robert L. Ullrich

Radiation-induced instability and its relation to radiation carcinogenesis.