Tani Shusuke, Blyth Benjamin John, Shang Yi, Morioka Takamitsu, Kakinuma Shizuko, Shimada Yoshiya
Department of Radiation Effects Research, National Institute of Radiological Sciences, Chiba, Japan.
J Cancer Prev. 2016 Jun;21(2):115-20. doi: 10.15430/JCP.2016.21.2.115. Epub 2016 Jun 30.
The risk of radiation-induced cancer adds to anxiety in low-dose exposed populations. Safe and effective lifestyle changes which can help mitigate excess cancer risk might provide exposed individuals the opportunity to pro-actively reduce their cancer risk, and improve mental health and well-being. Here, we applied a mathematical multi-stage carcinogenesis model to the mouse lifespan data using adult-onset caloric restriction following irradiation in early life. We re-evaluated autopsy records with a veterinary pathologist to determine which tumors were the probable causes of death in order to calculate age-specific mortality. The model revealed that in both irradiated and unirradiated mice, caloric restriction reduced the age-specific mortality of all solid tumors and hepatocellular carcinomas across most of the lifespan, with the mortality rate dependent more on age owing to an increase in the number of predicted rate-limiting steps. Conversely, irradiation did not significantly alter the number of steps, but did increase the overall transition rate between the steps. We show that the extent of the protective effect of caloric restriction is independent of the induction of cancer from radiation exposure, and discuss future avenues of research to explore the utility of caloric restriction as an example of a potential post-irradiation mitigation strategy.
辐射诱发癌症的风险增加了低剂量暴露人群的焦虑感。安全有效的生活方式改变有助于减轻额外的癌症风险，这可能为暴露个体提供主动降低癌症风险的机会，并改善心理健康和幸福感。在此，我们使用生命早期受辐照后成年期开始的热量限制，将数学多阶段致癌模型应用于小鼠寿命数据。我们与一位兽医病理学家重新评估了尸检记录，以确定哪些肿瘤可能是死亡原因，从而计算特定年龄的死亡率。该模型显示，在辐照和未辐照的小鼠中，热量限制在大部分寿命期间降低了所有实体瘤和肝细胞癌的特定年龄死亡率，由于预测的限速步骤数量增加，死亡率更多地取决于年龄。相反，辐照并没有显著改变步骤数量，但确实增加了步骤之间的总体转变率。我们表明，热量限制的保护作用程度与辐射暴露诱发癌症无关，并讨论了未来的研究途径，以探索将热量限制作为潜在辐照后缓解策略的一个例子的效用。
