Nakamura Nori
Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan.
Int J Radiat Biol. 2024;100(6):824-833. doi: 10.1080/09553002.2024.2338516. Epub 2024 Apr 22.
It has long been thought that the carcinogenic effect of radiation resulted from the induction of oncogenic mutations which then led to an increase in the proportion of cancer-bearing individuals. However, even as early as the 1960s, there were indications that the carcinogenic effect of radiation might result from the induction of an earlier onset of cancer. Recently, the former notion was challenged by its inability to explain time-dependent decline of the relative risk following an exposure to radiation, and a parallel shift of mouse survival curves toward younger ages following an exposure to radiation. The two observations are clearly understood if it is assumed only that a radiation exposure causes an earlier onset of spontaneously occurring cancers.
In the present study, a critical review was conducted which examined papers that showed dose responses which apparently supported the mutation induction theory of radiation carcinogenesis.
It was found that there were two types of misleading experimental designs: one consisted of studies in which observations were prematurely terminated, and which consequently hid a complete story of radiation carcinogenesis. The other set of papers used age adjustments which were derived from the idea that the life shortening effect of radiation needs to be compensated for since tumor mortality becomes higher among older subjects. This type of adjustment appeared reasonable but was found actually to be a different form of description on an earlier onset of cancer following radiation exposures.
In mouse experiments, radiation exposures did not lead to the induction of a large increase in the proportion of tumor deaths when life-long observations were made. Human epidemiologic data are also in line with the earlier onset hypothesis of radiation action. It should be cautioned, however, that the earlier onset model applies only to malignancies whose mortality increases rapidly with the increase of age and does not apply to diseases of short latency such as childhood leukemia and thyroid cancers.
长期以来，人们一直认为辐射的致癌作用源于致癌突变的诱导，进而导致患癌个体比例增加。然而，早在20世纪60年代就有迹象表明，辐射的致癌作用可能源于癌症发病时间提前。最近，前一种观点受到了挑战，因为它无法解释辐射暴露后相对风险随时间的下降，以及辐射暴露后小鼠生存曲线向年轻年龄的平行移动。如果仅假设辐射暴露会导致自发发生的癌症发病时间提前，那么这两个观察结果就能得到清楚的解释。
在本研究中，进行了一项批判性综述，审查了那些显示剂量反应的论文，这些反应显然支持辐射致癌的突变诱导理论。
发现有两种误导性的实验设计：一种是研究过早终止观察，从而掩盖了辐射致癌的完整情况。另一组论文使用了年龄调整，其依据是辐射的寿命缩短效应需要得到补偿，因为老年受试者的肿瘤死亡率更高。这种调整看似合理，但实际上被发现是对辐射暴露后癌症发病时间提前的另一种描述形式。
在小鼠实验中，进行终身观察时，辐射暴露并未导致肿瘤死亡比例大幅增加。人类流行病学数据也与辐射作用的发病时间提前假说一致。然而，需要注意的是，发病时间提前模型仅适用于死亡率随年龄增长迅速增加的恶性肿瘤，不适用于潜伏期短的疾病，如儿童白血病和甲状腺癌。
