Mayak工人肺癌发生的两阶段模型之外：对肺癌风险的影响
Beyond two-stage models for lung carcinogenesis in the Mayak workers: Implications for Plutonium risk
摘要：
机制多阶段模型被用来分析肺癌死亡率后，在马亚克工人队列中，随访至2008年的钚暴露。除了已建立的两阶段克隆扩张模型外，还研究了三个突变阶段的模型以及一个具有两条不同致癌途径的模型。结果表明，三阶段模型提供了一个改进的数据描述。最佳拟合模型指出了辐射增加克隆扩张速率的机制。这被解释为细胞周期控制的变化，由旁观者信号或细胞杀伤后的再增殖介导。没有统计证据的双途径模型被发现。为了阐明不同的辐射风险模型的含义，几个曝光场景进行了研究。在早期阶段具有辐射效应的模型显示出延迟的反应，并且在暴露时随着年龄的增长而明显下降。此外，剂量-反应关系是强非线性的所有三阶段模型，揭示了一个显着的增加超过临界剂量。
英文摘要：
Mechanistic multi-stage models are used to analyze lung-cancer mortality after Plutonium exposure in the Mayak-workers cohort, with follow-up until 2008. Besides the established two-stage model with clonal expansion, models with three mutation stages as well as a model with two distinct pathways to cancer are studied. The results suggest that three-stage models offer an improved description of the data. The best-fitting models point to a mechanism where radiation increases the rate of clonal expansion. This is interpreted in terms of changes in cell-cycle control mediated by bystander signaling or repopulation following cell killing. No statistical evidence for a two-pathway model is found. To elucidate the implications of the different models for radiation risk, several exposure scenarios are studied. Models with a radiation effect at an early stage show a delayed response and a pronounced drop-off with older ages at exposure. Moreover, the dose-response relationship is strongly nonlinear for all three-stage models, revealing a marked increase above a critical dose.
机构、总结、中文摘要均由AI分析而来，可能存在错误，请以论文正文为准。
