Center for Radiological Research, Columbia University Medical Center, New York, New York 10032, USA.
Radiat Res. 2010 Sep;174(3):357-66. doi: 10.1667/RR2143.1.
Studies of radiation carcinogenesis in animals allow detailed investigation of how the risk depends on age at exposure and time since exposure and of the mechanisms that determine this risk, e.g., induction of new pre-malignant cells (initiation) and enhanced proliferation of already existing pre-malignant cells (promotion). To assist the interpretation of these patterns, we apply a newly developed biologically based mathematical model to data on several types of solid tumors induced by acute whole-body radiation in mice. The model includes both initiation and promotion and analyzes pre-malignant cell dynamics on two different time scales: comparatively short-term during irradiation and long-term during the entire life span. Our results suggest general mechanistic similarities between radiation carcinogenesis in mice and in human atomic bomb survivors. The excess relative risk (ERR) in mice decreases with age at exposure up to an exposure age of 1 year, which corresponds to mid-adulthood in humans; the pattern for older ages at exposure, for which there is some evidence of increasing ERRs in atomic bomb survivors, cannot be evaluated using the data set analyzed here. Also similar to findings in humans, initiation dominates the ERR at young ages in mice, when there are few background pre-malignant cells, and promotion becomes important at older ages.
动物辐射致癌研究允许详细调查风险如何取决于暴露时的年龄和暴露后的时间，以及决定这种风险的机制，例如，诱导新的癌前细胞（引发）和增强已经存在的癌前细胞的增殖（促进）。为了帮助解释这些模式，我们将新开发的基于生物学的数学模型应用于在小鼠中由急性全身辐射引起的几种实体瘤的数据。该模型包括引发和促进作用，并在两个不同的时间尺度上分析癌前细胞动力学：在照射期间相对较短的时间内和整个寿命期间较长的时间内。我们的结果表明，小鼠的辐射致癌与人类原子弹幸存者之间存在普遍的机制相似性。暴露年龄的超额相对风险（ERR）在暴露年龄达到 1 岁时随着年龄的增长而降低，这相当于人类的成年中期；对于年龄较大的暴露年龄，有一些证据表明原子弹幸存者的 ERR 增加，但不能使用这里分析的数据来评估。与人类的发现相似，在小鼠中，当背景癌前细胞较少时，引发在年轻时主导 ERR，而促进作用在年龄较大时变得重要。
