Kai M, Luebeck E G, Moolgavkar S H
Department of Radiological Health, Faculty of Medicine, The University of Tokyo, Japan.
Radiat Res. 1997 Oct;148(4):348-58.
A two-stage stochastic model for carcinogenesis was used to analyze the incidence of cancer of the lung, stomach and colon in the cohort of atomic bomb survivors. We fitted the model assuming that acute exposure to radiation results in the creation of initiated cells that are added to the pool of spontaneously initiated cells. In the cancers analyzed, with the exception of lung cancer in females, we found no evidence that radiation-induced initiation was dependent upon age at exposure. In contrast, we found that spontaneous initiation was dependent upon age at exposure in the cancers analyzed except stomach cancer among males. Because exposure to radiation in this cohort occurred at the same time for all members of the cohort, age at exposure is exactly correlated with birth cohort, and the dependence of spontaneous initiation on age at exposure is a reflection of the cohort effects seen in these cancers in Japan. Even without a dependence of radiation-induced initiation on age at exposure, the two-stage model can explain the temporal behavior of the excess relative risk with age at exposure and time since exposure. In particular, the model predicts that excess relative risk is highest among those exposed as children. Moreover, since radiation-induced initiation is not higher among those exposed as children, the excess relative risk in this group is not due to an inherently higher sensitivity to radiation. Our biologically based approach provides another perspective on the temporal behavior of risk after acute exposure to ionizing radiation.
采用两阶段随机致癌模型分析原子弹爆炸幸存者队列中肺癌、胃癌和结肠癌的发病率。我们拟合该模型时假定,急性辐射暴露会导致产生起始细胞,这些细胞会加入到自发产生的起始细胞库中。在所分析的癌症中,除了女性肺癌外,我们没有发现证据表明辐射诱导的起始作用依赖于暴露时的年龄。相反,我们发现,在所分析的癌症中,除了男性胃癌外,自发起始作用依赖于暴露时的年龄。由于该队列中的所有成员同时受到辐射暴露,暴露时的年龄与出生队列完全相关,自发起始作用对暴露时年龄的依赖性反映了在日本这些癌症中观察到的队列效应。即使辐射诱导的起始作用不依赖于暴露时的年龄,两阶段模型也可以解释暴露时年龄和暴露后时间与超额相对风险的时间行为。特别是,该模型预测,儿童时期受辐射暴露者的超额相对风险最高。此外,由于儿童时期受辐射暴露者的辐射诱导起始作用并不更高,该组的超额相对风险并非由于对辐射的固有更高敏感性。我们基于生物学的方法为急性暴露于电离辐射后的风险时间行为提供了另一种视角。