The effect of low-dose ionizing radiation exposure on leukemia incidence remains poorly understood. Possible dose-response curves for various forms of leukemia are largely based on cohorts of atomic bomb survivors. Animal studies can contribute to an improved understanding of radiation-induced acute myeloid leukemia (rAML) in humans. In male CBA/H mice, incidence of rAML can be described by a two-hit model involving a radiation-induced deletion with Sfpi1 gene copy loss and a point mutation in the remaining Sfpi1 allele. In the present study (historical) mouse data were used and these processes were translated into a mathematical model to study photon-induced low-dose AML incidence in male CBA/H mice following acute exposure. Numerical model solutions for low-dose rAML incidence and diagnosis times could respectively be approximated with a model linear-quadratic in radiation dose and a normal cumulative distribution function. Interestingly, the low-dose incidence was found to be proportional to the modeled number of cells carrying the Sfpi1 deletion present per mouse following exposure. After making only model-derived high-dose rAML estimates available to extrapolate from, the linear-quadratic model could be used to approximate low-dose rAML incidence calculated with our mouse model. The accuracy in estimating low-dose rAML incidence when extrapolating from a linear model using a low-dose effectiveness factor was found to depend on whether a data transformation was used in the curve fitting procedure.

低剂量电离辐射暴露对白血病发病率的影响仍然知之甚少。各种形式的白血病可能的剂量反应曲线主要基于原子弹幸存者的队列。动物研究可以帮助人们更好地理解辐射诱发的人类急性髓细胞性白血病（rAML）。在雄性CBA / H小鼠中，rAML的发生可以通过两次打击模型来描述，该模型涉及辐射诱发的缺失Sfpi1基因拷贝丢失和其余Sfpi1等位基因中的点突变。在本研究中（历史），使用了小鼠数据，并将这些过程转换为数学模型，以研究光子诱导的急性暴露后雄性CBA / H小鼠的低剂量AML发生率。低剂量rAML发生率和诊断时间的数值模型解可以分别用辐射剂量线性二次模型和正态累积分布函数来近似。有趣的是，发现低剂量发生率与暴露后每只小鼠携带Sfpi1缺失的模型细胞数量成正比。在仅提供模型推断的高剂量rAML估计值以进行推断后，可以使用线性二次模型来近似计算用我们的小鼠模型计算出的低剂量rAML发生率。发现使用低剂量有效性因子从线性模型外推时估计低剂量rAML发生率的准确性取决于曲线拟合过程中是否使用了数据转换。