QUANTITATIVE STUDIES OF ONCOGENIC TRANSFECTION

致癌转染的定量研究

• 批准号: 6587298
• 负责人: ERIC J HALL
• 金额: $ 24.33万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-18 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6587298
• 关键词: alpha radiation; cancer risk; chemical related neoplasm /cancer; gene expression; genetically modified animals; laboratory mouse; microarray technology; neoplasm /cancer genetics; neoplastic transformation; radiation carcinogenesis; radiation related neoplasm /cancer; radiobiology; radon; southern blotting; tissue /cell culture; transfection

DESCRIPTION: (Applicant's Description) In vitro assays for oncogenic transformation based on rodent cells represent a powerful research tools for investigating radiation carcinogenesis. First, they are highly quantitative; this is true for both C3H, 10T1/2 cells and fresh explants of mouse embryo cells. Second, the influence of specific genes on radiation induced transformation can be studied by using embryo cells. Second, the influence of specific genes on radiation induced transformation can be studied by using embryo cells from knock-out mice. Transformation assays based on human cells are not as quantitative, but are more relevant for seeking genes involved in the oncogenic process. Five questions will be addressed, all of which relate directly to the primary overall goal of this program project, namely an understanding of the mechanisms of alpha-particle induced oncogenesis. (1) Can transformation be induced in cells in which the cytoplasm has been traversed by one or more alpha-particles, but none have penetrated the nucleus? (2) Is there a "bystander effect" for transformation- i.e. can transformation can induced in cells which are not directly hit, but are in contact and the communication with cells suffering trans-nuclear or trans- cytoplasmic alpha-particles transversals? What are the conditions for the bystander effect to be manifest? (3) Does the transformation incidence resulting from a pair of alpha-particles through the cell nucleus depend on the spatial and temporal separation of the particles? (4) Does the incidence of transformation induced by alpha-particles in mouse embryo cells depend on the status of the ATM gene? (5) Are specific genes consistently unregulated or down-regulated in human cells transformed by alpha-particles.

描述：（申请人的描述）基于啮齿动物细胞的致癌转化的体外测定代表了研究辐射癌变的强大研究工具。首先，它们是高度定量的。对于C3H，10T1/2细胞和小鼠胚胎细胞的新鲜外植体都是如此。其次，可以使用胚细胞研究特定基因对辐射诱导转化的影响。其次，可以通过使用敲除小鼠的胚细胞来研究特定基因对辐射诱导转化的影响。基于人类细胞的转化分析不是定量的，而是寻求与致癌过程有关的基因更相关。将解决五个问题，所有这些问题都与该计划项目的主要总体目标直接相关，即对α粒子诱导的肿瘤发生的机制有所了解。 （1）可以在细胞质通过一个或多个α粒子穿过的细胞中诱导转化，但没有一个渗透核？ （2）转化是否存在“旁观者效应” - 即可以在不直接命中但正在接触的细胞中引起的转化，并且与患有跨核或经胞质α粒子的细胞的通信？旁观者效应表现出什么条件？ （3）通过一对α粒子通过细胞核引起的转化发生率是否取决于颗粒的空间和时间分离？ （4）小鼠胚胎细胞中α粒子引起的转化的发生率是否取决于ATM基因的状态？ （5）在由α粒子转化的人类细胞中始终不受管制或下调的特定基因。