Department, of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Int J Radiat Biol. 2021;97(10):1341-1351. doi: 10.1080/09553002.2021.1955998. Epub 2021 Jul 26.
Ionizing radiation is a well-known carcinogen, and epidemiologic efforts have been made to evaluate cancer risks following a radiation exposure. The basic approach has been to estimate increased levels of cancer mortality resulting from exposures to radiation, which is consistent with the somatic mutation theory of cancer. However, the possibility that an irradiation might cause an earlier onset of cancer has also been raised since the earliest days of animal studies. Recently, the mutation induction model has been challenged because it is unable to explain the observed dose-related shift of entire mouse survival curves toward younger ages following an irradiation. This is because if it is assumed that only a fraction of the irradiated individuals are affected, the irradiated population would consist of two subpopulations with different mean lifespans, which makes the overall distribution of individual lifespans broader, and hence the slope of the survival curves shallower. To explain this parallel shift, it is necessary to assume that individuals of a population are affected. As a result of these observations, possible mechanisms which could account for the parallel shift of mouse survival curves were sought by examining the radiation induction of various types of tissue damage which could facilitate an earlier onset of spontaneously arising cancers.
A proposed mechanism postulates that a radiation exposure leads to tissue inflammation which subsequently stimulates spontaneously arising cancers and allows them to appear earlier than usual. This notion is not unprecedented, and because the background incidence of cancer increases exponentially with an increase in age, a slight shift of the onset age toward younger ages may make it appear as if the risk is increased. In this scenario, a radiation exposure induces DNA damage, cell death, chromosome aberrations etc., which leads to the multi-pathway responses including activation of stromal fibroblasts, macrophages and various inflammatory factors. Such an inflamed microenvironment favors the growth of spontaneously arising tumor cells although currently, the sequential order or relative importance of the individual factors remains to be known.
电离辐射是一种已知的致癌物质，为了评估辐射暴露后的癌症风险，流行病学研究已经进行。基本方法是估计因暴露于辐射而导致的癌症死亡率增加，这与癌症的体细胞突变理论一致。然而，自从动物研究的早期开始，就已经提出了辐射可能导致癌症更早发生的可能性。最近，由于突变诱导模型无法解释在照射后整个小鼠存活曲线向更年轻年龄的观察到的剂量相关转移，该模型受到了挑战。这是因为如果假设只有一部分受照射的个体受到影响，那么受照射的人群将由两个具有不同平均寿命的亚群组成，这使得个体寿命的总体分布更宽，因此生存曲线的斜率更浅。为了解释这种平行转移，有必要假设群体中的个体受到影响。由于这些观察结果，通过检查可能导致小鼠存活曲线平行转移的各种类型的组织损伤的辐射诱导，寻求了可能解释这种现象的机制。
提出的机制假设辐射暴露会导致组织炎症，随后刺激自发发生的癌症，并使它们比通常更早出现。这个概念并不是前所未有的，由于癌症的背景发生率随着年龄的增加呈指数增长，因此发病年龄的轻微转移可能会使风险看起来增加。在这种情况下，辐射暴露会导致 DNA 损伤、细胞死亡、染色体畸变等，从而导致包括基质成纤维细胞、巨噬细胞和各种炎症因子激活的多途径反应。这种炎症微环境有利于自发发生的肿瘤细胞的生长，尽管目前，单个因素的顺序或相对重要性仍有待了解。
