Department of Pathology, Institute of Development, Aging and Cancer, Tohoku University, Japan.
Health Phys. 2010 Sep;99(3):388-93. doi: 10.1097/HP.0b013e3181cd4153.
Irradiation from internally deposited radionuclides induces malignant tumors. Ingested radionuclides accumulate in specific organs, which are irradiated over a lifelong period. Our aim is to elucidate why the development of malignant tumors requires long-term internal exposure, on the order of decades, despite the fact that irradiation is continuous over this period. Three major factors are considered to be responsible for the long incubation time in carcinogenesis caused by internally deposited alpha-emitters: uneven distribution of radionuclides, limited range of irradiation, and dynamic movement of tumor precursor cells. We hypothesized that target cells susceptible to malignant transformation may undergo one event by alpha particles and may then migrate outside of the range of alpha particles, thereby avoiding immediate induction of successive additional events that would lead to cell death or neoplastic changes. Based on this hypothesis, we further proposed a mathematical model to predict the relationship between dose rate and incubation period of tumors induced by internally deposited alpha-emitters. The function was non-linear and included terms of both direct and indirect radiation effects. It well fitted both human Th-ICC cases and rat Pu-induced lung cancer, suggesting that indirect radiation effects are independent from dose rate. The significance of parameters of the model is discussed.
内照射放射性核素会诱发恶性肿瘤。摄入的放射性核素会在特定器官中积累,并在整个生命周期中受到辐射。我们的目的是阐明为什么尽管在此期间持续辐射,但恶性肿瘤的发展仍需要数十年的长期内部暴露。有三个主要因素被认为是导致内照射α发射体致癌潜伏期长的原因:放射性核素分布不均匀、照射范围有限和肿瘤前体细胞的动态运动。我们假设,易发生恶性转化的靶细胞可能会受到α粒子的一次作用,然后迁移到α粒子的照射范围之外,从而避免立即引发导致细胞死亡或肿瘤变化的连续附加事件。基于这一假设,我们进一步提出了一个数学模型来预测内照射α发射体诱发肿瘤的剂量率与潜伏期之间的关系。该函数是非线性的,包括直接和间接辐射效应的项。它很好地拟合了人类 Th-ICC 病例和大鼠 Pu 诱导的肺癌,表明间接辐射效应与剂量率无关。模型参数的意义将进行讨论。