QUANTITATIVE STUDIES OF ONCOGENIC TRANSFECTION

基于啮齿动物细胞的体外致癌转化实验 为研究致癌因素提供了一个强有力的研究工具 在环境中发现的物理和化学制剂的潜力，因为 它们是高度量化的。C3H10T 1/2尤其如此 细胞。 将解决三个问题，所有这些问题都与初级总体 计划项目的目标。首先，转型发生率将是 准确评估1、2、4或8个阿尔法粒子(90和180ke V/mU) 与相同Leta粒子的泊松分布数的比较 平均遍历次数为1、2、4或8。这将解决 在国内支气管炎情况下评估癌症风险的问题 从本质上讲，上皮细胞不会被一个以上的颗粒穿过， 通过从地下矿工数据进行外推，其中有多个导线 很普通。第二，将进行实验，以考察其对 α粒子与α粒子相互作用的相变关联 存在于地下矿山粉尘中的亚砷酸盐。地下 矿工同时接触到所有这些致癌物质。在 在砷的情况下，暴露只发生在矿山，而不是在家庭中，因此 所有需要做的就是了解交互模式--所以 这可以考虑到矿工在氡之前的亚砷酸盐效应。 风险被外推到国内情况。相比之下，在这种情况下 对于烟草特有的亚硝胺，还必须知道 同时接触a粒子和亚硝胺会影响这一过程。 从高剂量到低剂量的α粒子外推，因为虽然 基本上所有矿工都吸烟，国内情况包括这两种情况 吸烟者和非吸烟者。第三，转型的发生率将是 与给定的五个a粒子的平均值相比，要么是单个 细胞的生成，或作为每一代一个粒子。这解决了 问题是大多数地下矿工的目标细胞，其风险是 被外推到低剂量，被暴露在许多细胞中 因此多个a粒子的遍历将受到 细胞及其后代，而不是单个细胞。来自所有这三个地方的数据 AIMS将对获取肺癌风险的实际问题产生影响 从剂量学或流行病学对家庭中氡的估计 接近了。它们将被整合到项目I的模型中。

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.