QUANTITATIVE STUDIES OF ONCOGENIC TRANSFECTION

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， 环境中发现的物理和化学物质的潜力， 它们是高度定量的。 C3 H 10 T 1/2尤其如此 细胞 将讨论三个问题，所有这些问题都与主要的总体问题有关。 方案项目的目标。 首先，转换发生率将是 准确评估1、2、4或8个α粒子（LET 90和180 keV/mu） 与相同LET的α粒子泊松分布数相比， 平均遍历数为1、2、4或8。 这将解决 在支气管哮喘的家庭环境中评估癌症风险的问题 上皮细胞基本上不会被一个以上的颗粒穿过， 通过从地下采矿机数据进行外推， 共同 第二，将进行实验以研究对 a粒子之间相互作用的转变入射率， 地下矿井粉尘中存在的亚砷酸盐。 地下 矿工同时接触所有这些致癌物。 在 就砷酸盐而言，接触仅发生在矿井中，而不是在家中，因此， 所需要的只是对交互模式的理解--因此， 考虑到砷对矿工的影响， 风险被推断到国内情况。 相比之下， 烟草特有的亚硝胺，也很重要的是要知道， 同时暴露于a粒子和亚硝胺会影响这一过程 从高剂量到低剂量的a粒子外推，因为 基本上所有矿工都吸烟，国内情况包括两者 吸烟者和不吸烟者。 第三，转化发生率将是 对于给定的五个a粒子的平均值， 每代细胞，或每代一个颗粒。 这解决了 问题是，大多数地下矿工的目标细胞，其风险是 外推到低剂量，暴露在许多细胞 因此，A粒子的多次穿越将由一个 细胞及其后代，而不是单个细胞。 所有三个数据 目的将影响获得肺癌风险的实际问题 从剂量学或流行病学的角度估计家庭中的氡 接近。 它们将被纳入项目一的建模工作。

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.