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

致癌作用的数学模型阐明辐射诱发癌症的机制

基本信息

批准号：
11680555
负责人：
KAI Michiaki
金额：
$ 2.43万
依托单位：
Oita University of Nursing and Health Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680555/
关键词：
Multistage model atomic bomb survivors genomic instability DNA damage low dose and dose-rate 原爆被爆者

项目摘要

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.

在之前的辐射相关癌症机制范式中，DMA 直接损伤引起的突变事件可能引发癌症。多阶段建模有助于了解癌症的诱发。在最近的多阶段模型研究中，原子弹幸存者的流行病学数据对于分析辐射致癌非常有用。最近的生物学数据表明，辐射诱发的直接突变不是直接突变，而是间接突变与辐射致癌有关。基因组不稳定现象可能会改变我们对低剂量和剂量率反应的理解。此外，验证辐射生物学的含义可能非常有趣，基因组不稳定性是否会导致癌变。基因组不稳定性假说可以提供辐射致癌的示意图。基于该假说，将利用广岛和长崎的原子弹幸存者数据开发和分析考虑基因组不稳定性的致癌模型。如果我们查看 1987 年之前的原子弹幸存者数据，就不会拒绝基因组不稳定性是否与辐射致癌有关的假设。对该队列的进一步随访对于模型的验证至关重要。