Brenner D J, Sachs R K
Center for Radiological Research, Columbia University, 630 West 168th Street, New York, NY 10032, USA.
Int J Radiat Biol. 2002 Jul;78(7):593-604. doi: 10.1080/09553000210121740.
Radon risks derive from exposure of bronchio-epithelial cells to high-linear energy transfer (LET) alpha-particles. alpha-particle exposure can result in bystander effects, where irradiated cells emit signals resulting in damage to nearby unirradiated bystander cells. This can result in non-linear dose-response relations, and inverse dose-rate effects. Domestic radon risk estimates are currently extrapolated from miner data, which are at both higher doses and higher dose-rates, so bystander effects on unhit cells could play a large role in the extrapolation of risks from mines to homes. Therefore, we extend an earlier quantitative mechanistic model of bystander effects to include protracted exposure, with the aim of quantifying the significance of the bystander effect for very prolonged exposures.
A model of high-LET bystander effects, originally developed to analyse oncogenic transformation in vitro, is extended to low dose-rates. The model considers radiation response as a superposition of bystander and linear direct e It attributes bystander effects to a small subpopulation of hypersensitive cells, with the bystander contribution dominating the direct contribution at very low acute doses but saturating as the dose increases. Inverse dose-rate effects are attributed to the replenishment of the hypersensitive subpopulation during prolonged irradiation.
The model was fitted to dose- and dose-rate-dependent radon-exposed miner data, suggesting that one directly hit target bronchio-epithelial cell can send bystander signals to about 50 neighbouring target cells. The model suggests that a naïve linear extrapolation of radon miner data to low doses, without accounting for dose-rate, would result in an underestimation of domestic radon risks by about a factor of 4, a value comparable with the empirical estimate applied in the recent BEIR-VI report on radon risk estimation.
Bystander effects represent a plausible quantitative and mechanistic explanation of inverse dose-rate effects by high-LET radiation, resulting in non-linear dose-response relations and a complex interplay between the effects of dose and exposure time. The model presented provides a potential mechanistic underpinning for the empirical exposure-time correction factors applied in the recent BEIR-VI for domestic radon risk estimation.
氡气风险源于支气管上皮细胞暴露于高传能线密度（LET）的α粒子。α粒子暴露可导致旁观者效应，即受辐照细胞发出信号，致使附近未受辐照的旁观者细胞受损。这会导致非线性剂量反应关系以及剂量率反比效应。目前国内氡气风险评估是根据矿工数据外推得出的，而矿工所受剂量和剂量率都更高，因此旁观者效应在从矿井到家庭的风险外推中可能起很大作用。所以，我们扩展了早期关于旁观者效应的定量机制模型，将长期暴露纳入其中，目的是量化旁观者效应在极长时间暴露情况下的重要性。
一个最初用于分析体外致癌转化的高LET旁观者效应模型被扩展至低剂量率情况。该模型将辐射反应视为旁观者效应和线性直接效应的叠加。它将旁观者效应归因于一小部分超敏细胞，在极低急性剂量下旁观者效应的贡献占主导，但随着剂量增加而饱和。剂量率反比效应归因于长期辐照期间超敏亚群的补充。
该模型与依赖剂量和剂量率的氡暴露矿工数据拟合，表明一个直接命中的目标支气管上皮细胞可向约50个相邻目标细胞发送旁观者信号。该模型表明，在不考虑剂量率的情况下，将氡矿工数据简单线性外推至低剂量，会导致低估家庭氡气风险约4倍，这一数值与近期关于氡风险评估的BEIR - VI报告中应用的经验估计值相当。
旁观者效应为高LET辐射导致的剂量率反比效应提供了一个合理的定量和机制解释，导致非线性剂量反应关系以及剂量效应和暴露时间效应之间的复杂相互作用。所提出的模型为近期BEIR - VI用于家庭氡气风险评估的经验暴露时间校正因子提供了潜在的机制基础。
