Mathematical modeling in carcinogenesis to elucidate the mechanism of radiation-induced cancer

在先前的辐射相关癌症机制范例中，由于直接损伤DMA而导致的突变事件可能引发癌症。多阶段建模有助于理解癌症的诱导。在多阶段模型的研究中，原子弹爆炸幸存者的流行病学数据对于分析辐射致癌作用是非常有用的，最近的生物学数据表明，辐射诱发的直接突变而是间接突变与辐射致癌作用有关。基因组不稳定现象可能会改变我们对低剂量和剂量率响应的理解。此外，它可能是非常感兴趣的，以验证从辐射生物学的暗示是否基因组不稳定性有助于致癌与否。基因组不稳定性假说可以提供辐射致癌的示意图，基于这一假说，我们将建立考虑基因组不稳定性的致癌模型，并利用广岛和长崎的原子弹幸存者数据进行分析。如果我们看看1987年以前的原子弹爆炸幸存者数据，我们就不会否定基因组不稳定性是否与辐射致癌有关的假设。对该队列的进一步跟踪对于验证模型至关重要。

In the previous paradigm for mechanism of radiation-related cancer, mutational events due to direct damage to DMA could cause initiation leading to cancer. Multistage modeling can contribute to an understanding of the induction of cancer. In recent studies on multistage modeling, the epidemiological data of atomic bomb survivors are very useful for analyzing radiation carcinogenesis.Recent biological data indicate that not direct mutation induced by radiation but indirect mutation would be relevant to radiation carcinogenesis. The phenomena of genomic instability may change our understanding of low dose and dose-rate response. In addition, it may be of much interest to verify an implication from radiation biology whether genomic instability contributes to carcinogenesis or not. A genomic instability hypothesis can provide a schematic diagram of radiation carcinogenesis.Based on this hypothesis, carcinogenesis models considering genomic instability will be developed and analyzed using the atomic bomb survivor data in Hiroshima and Nagasaki. The hypothesis whether genomic instability is relevant to radiation carcinogenesis is not rejected if we look at the atomic bomb survivor data until 1987. Further follow-up of the cohort will be essential to validation of the models.