Methematical Modeling of Carcinogenesis

Niwa等人分析了辐照^<252>Cf的父亲小鼠和未辐照的母亲小鼠所生的F1小鼠的一个高变小卫星位点的父系服务等位基因的种系突变频率。显著的过量风险因辐照而延长，在世代遗传不稳定，因辐照暴露的细胞被检测为精细胞期。^<252>Cf辐射对精子期生殖系细胞诱导突变的剂量响应在0.7Gy以下呈线性。他们得出结论，DNA损伤不是该位点突变的直接原因，但它可能引起遗传不稳定，从而导致高可变小卫星位点的重组。（Niwa et al., j .辐射研究37,1996）。Ohtaki将癌变看作一个细胞的突变、突变细胞的增殖、恶性细胞的出现、肿瘤的形成和生长等一系列事件，提出了一种数学模型，称为“Premutation”-Mutation模型。在这个模型中，假设只有癌变的第一步可能有暴露依赖性，肿瘤生长周期的长度被表述为一个随机变量，这个随机变量可能非常超过个体。将该模型应用于辐射效应研究基金会发表的广岛和长崎原子弹幸存者的癌症发病率数据和小鼠的致癌数据，并对剂量-反应关系进行了统计分析（Ohtaki，《广岛医学杂志》，1996年第49期）。Matsuura等人分析了生活在广岛县的原子弹幸存者的死亡率数据。他们假设辐照剂量与各种癌症致死风险呈线性剂量-反应关系，并运用动态队列研究技术对数据进行分析。结果，在暴露人群中，白血病、肺癌、结肠癌和乳腺癌的死亡率在统计上存在显著的超额风险。（Matsuura et al., Journal of Radiation Research，已出版）。少

Niwa et al.analyzed the frequency of germline mutation at the pathernally serived allele of a hypervariable minisatellite locus for F1 mice which were born between the father mice which irradiated ^<252>Cf and unirradiated mother mice. A significant excess risk due to the irradiation, extended in the generation inherited unstable because of the radiation exposure of the cell was detected for spermatid stage. The dose response of ^<252>Cf radiation for induction of germline mutation was linear up to 0.7Gy for spermatid stage germ line cells. They concluded that DNA damage is not the direct cause of mutations at this locus, but it may induce genetic instability which in turn induces recombination at the hypervariable minisatellite locus. (Niwa et al., J.Radiation Research 37,1996).Regarding the carcinogenesis as a series of events of mutation of one cell, proliferation of the mutation cell, the appearance of the malignant cell and the formation and the growth of tumor, Ohtaki developed t … More he mathematical model which was called "Premutation" -Mutation model. In this model, it is assumed that only the first step of carcinogenesis may have the exposure dependency and the length of the tumor growth period is formulated as a random variable which may very over individuals. The model was applied to the cancer incidence data in the Atomic bomb Survivors in Hiroshima and Nagasaki which were published from Radiation Effects Reasearch Foundation and to the mice's carcinogenesis data, and the dose-response relationship was analyzed statistically (Ohtaki, Hiroshima Medical Journal 49,1996).Matsuura et al.analyzed the data of the mortality rate among Atomic bomb Survivors living in Hiroshima Prefecture. Assuming linear dose-response relationship between the exposed radiation dose and motality risk from various cancers, and appling the technique of the dynamic cohort study, they analyzed the data. As a result, statistically significant excess risk among exposed population was detected for mortality from leukemia, the lung cancer, colon cancer, and breast cancer. (Matsuura et al., Journal of Radiation Research, in press). Less