RADIATION BIOLOGY OF SIMULATED RADON DAUGHTER ALPHAS

与国内氡有关的美国年度死亡率的合理估计 暴露量从0到40，000不等。 这种广泛的范围很大程度上是由于 各种假设和推断的不确定性， 进行基于流行病学的风险评估。 这个项目带来了 在实验辐射生物学中， 一个强大的理论框架提供了一个建模项目;它是 具体针对减少外推中的不确定性， 特别是从高剂量到低剂量，从高剂量率到低剂量率，以及 不同的辐射质量。 根据对来源的详细分析， 在估计国内氡风险的不确定性，我们的五个目标是 1)了解如何将氡风险推断到非常低的剂量， 对应于每个单元小于一个a颗粒的平均值; 2)氡的适当品质因数的评估; 3)α粒子暴露时间重要性的鉴定 4)α粒子与其它肺的相互作用研究 致癌物质; 5)a粒子暴露的特征性生物标志物研究。 由于人类研究终点的随机性， (lung癌症），我们的三个体外实验项目专注于突变， 染色体畸变和致癌转化。 在每种情况下，我们 总体目标以国内氡风险评估的需要为指导， 建模项目旨在分析实验结果， 将结论应用于风险评估。 这项提议的一个关键组成部分是单粒子微束， 使得将精确数量的α粒子 细胞，包括单个粒子。 在过去的一年里， 我们可以将已知数量的a粒子输送到单个细胞的能力 一个数量级。 核心问题是评估癌症风险， 国内情况下，支气管上皮细胞， 基本上一生中从未被超过一个a粒子穿过， 根据地下采矿机数据进行外推， 共同 该建议的重点是使用微束与所有的 上述生物系统，进一步复杂化的因素是剂量 延长和其他致癌物质的存在。

Plausible estimates of the annual US mortality linked to domestic radon exposure vary from 0 to 40,000. This wide range is largely a result of uncertainties in the various assumptions and extrapolations necessary to produce an epidemiologically-based risk estimate. This project brings together and links three projects in experimental radiation biology, within a strong theoretical framework provided by a modelling project; it is specifically targeted ar reducing uncertainties in extrapolation, particularly from high to low dose, from high to low dose rate, and between different radiation qualities. Based on a detailed analysis of the sources of uncertainty in estimating domestic radon risk, our five goals are 1) Understanding how to extrapolate radon risks down to very low doses, corresponding to an average of less than one a particle per cell; 2) Assessment of appropriate quality factors for radon; 3) Evaluation of the significance of a-particle exposure time; 4) Investigation of the interaction between a-particles and other lung carcinogens; 5) Investigation of characteristic biomarkers of a-particle exposure. Because of the stochastic nature of the endpoint of interest in humans (lung cancer), our three in vitro experimental projects focus on mutation, chromosomal aberration and oncogenic transformation. In each case our overall aims are guided by the needs of domestic radon risk estimation, and the modelling project is designed to analyze the experimental results and apply the conclusions to risk estimation. A key component of this proposal is the single-particle microbeam, which makes it possible to deliver exact numbers of a-particles to individual cells, including a single particle. In the last year, the speed at which we can deliver known numbers of a particles to single cells has increased by an order of magnitude. The central issue is to assess cancer risks in the domestic situation where cells of the bronchial epithelium are essentially never traversed by more than one a-particle in a life-time, by extrapolation from underground miner data where multiple traversals are common. The focus of this proposal is to use the microbeam with all of the biological systems listed above, further complicating factors being dose prolongation and the presence of other carcinogens.