QUANTITATIVE STUDIES OF ONCOGENIC TRANSFECTION

致癌转染的定量研究

• 批准号: 6102521
• 负责人: ERIC J HALL
• 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/6102521
• 关键词: alpha radiation; arsenic; cancer risk; chemical carcinogenesis; chemical related neoplasm /cancer; clinical research; dust; human data; minings; neoplastic transformation; nitrosamines; radiation carcinogenesis; radiation related neoplasm /cancer; radiobiology; radiochemistry; radon; tissue /cell culture; tobacco

In vitro assays for oncogenic transformation based on rodent cells represent a powerful research tool for investigating the oncogenic potential of physical and chemical agents found in the environment because they are highly quantitative. This is particularly true of C3H 10T 1/2 cells. Three issues will be addressed, all of which relate to the primary overall goals of the program project. First, transformation incidence will be assessed for exactly 1, 2, 4 or 8 alpha-particles (LET 90 and 180 ke V/mu) compared with Poisson-distributed numbers of a-particles of the same LET and with mean traversal numbers of 1, 2, 4, or 8. This will address the question of assessing cancer risks in a domestic situation where bronchial epithelial cells are essentially never traversed by more than one particle, by extrapolation from underground miner data where multiple traversals are common. Second, experiments will be performed to investigate the effect on transformation incidence of the interaction between a-particles and arsenites which are present int he dust of underground mines. Underground miners were exposed concomitantly to all of these carcinogens. In the case of arsenates, exposure occurs only in mines and not in homes, so that all that is required is an understanding of the mode of interaction - so that allowance can be made for the arsenite effect in miners before radon risks are extrapolated to a domestic situation. By contrast, in the case of tobacco specific nitrosamines, it is also important to know if concurrent exposure to a-particles and nitrosamines influences the process of extrapolation from high to low doses of a-particles, since while essentially all miners smoked, the domestic situation includes both smokers and non-smokers. Third, the transformation incidence will be compared for a mean of five a-particles given, either to a single generation of cells, or as one particle per generation. This addresses the problem that the target cells in most underground miners, whose risks are to be extrapolated to low doses, were exposed over many cellular generations so that multiple a-particle traversals would be suffered by a cell and its progeny, rather than by a single cell. Data from all three aims will impact on the practical problem of obtaining lung cancer risk estimates for radon in homes from either the dosimetric or epidemiological approaches. They will be integrated into modelling in Project I.

基于啮齿动物细胞的致癌转化的体外测定 代表了一个强大的研究工具，用于研究致癌 在环境中发现的物理和化学剂的潜力，因为 它们是高度定量的。 C3H 10T 1/2尤其如此 细胞。 将解决三个问题，所有问题与主要整体有关 计划项目的目标。 首先，变换的发生率将是 精确评估1、2、4或8个α粒子（令90和180 ke V/MU） 与泊松分布的同一a粒子数量相比 并以1、2、4或8的平均遍历数。这将解决 在支气管中评估癌症风险的问题 上皮细胞本质上永远不会被多个粒子穿过， 通过从地下矿工数据中推断出多次遍历的数据 常见的。 其次，将进行实验以研究对 A粒子与 存在地下矿山的砷。 地下 矿工同时暴露于所有这些致癌物中。 在 砷的情况，暴露仅发生在地雷而不发生在房屋中，以便 所需的只是了解互动方式 - 因此 可以在矿工的砷效应之前允许 风险被推断到国内局势。 相比之下， 在特定烟草的亚硝胺中，也必须知道是否是否 同时接触A粒子和亚硝胺会影响该过程 从高剂量到低剂量的A粒子的外推 本质上是所有吸烟的矿工，国内局势包括 吸烟者和非吸烟者。 第三，转换的发生率将是 比较给出五个A粒子的平均值 细胞的产生，或每一代粒子。 这解决了 大多数地下矿工中的目标细胞的风险是 要外推到低剂量，在许多细胞上暴露 几代人，以使多个A粒子遍历 细胞及其后代，而不是单个细胞。 来自这三个的数据 目标将影响获得肺癌风险的实际问题 剂量学或流行病学的房屋中ra的估计值 方法。 它们将在项目I。