QUANTITATIVE STUDIES OF ONCOGENIC TRANSFECTION

基于啮齿动物细胞的致癌转化体外测定 代表了研究致癌性的强大研究工具 环境中发现的物理和化学试剂的潜力，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，所有这些问题都与主要整体有关 计划项目的目标。 首先，转化发生率为 精确评估 1、2、4 或 8 个 α 粒子（LET 90 和 180 ke V/mu） 与相同 LET 的 a 粒子的泊松分布数相比 平均遍历次数为 1、2、4 或 8。这将解决 评估支气管哮喘国内癌症风险的问题 上皮细胞基本上不会被超过一个粒子穿过， 通过从多次遍历的地下矿工数据推断 常见的。 其次，将进行实验来研究其影响 a-粒子之间相互作用的转变发生率 存在于地下矿井粉尘中的亚砷酸盐。 地下 矿工同时接触所有这些致癌物质。 在 就砷而言，接触仅发生在矿井中，而不是家庭中，因此 所需要的只是了解交互模式 - 所以 可以在氡气之前考虑到矿工中的亚砷酸盐效应 风险被推断到国内形势。 相比之下，在这种情况下 对于烟草特有的亚硝胺，了解是否存在也很重要 同时暴露于α粒子和亚硝胺会影响该过程 从高剂量到低剂量的 a 粒子的外推法，因为 基本上所有矿工都抽烟，国内情况包括 吸烟者和非吸烟者。 第三，转化发生率为 比较给定的五个 a 粒子的平均值，或者与单个 一代细胞，或作为每一代一个粒子。 这解决了 大多数地下矿工的目标细胞的问题，其风险是 推断为低剂量，暴露于许多细胞 世代，以便多次 a 粒子遍历将受到 细胞及其后代，而不是单个细胞。 来自所有三个的数据 目标将影响获取肺癌风险的实际问题 根据剂量学或流行病学方法对家庭中的氡气进行估计 接近。 它们将被集成到项目 I 的建模中。

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.