Abstract
Radiation-induced acute myeloid leukemia (AML) in C3H/HeN mice is an important animal experimental model to predict a human AML risk at low doses. The stem cells induced AML in mice usually carry a deletion of chromosome 2 and a mutation of the Sfpi1 gene on the retained homologue. These genetic changes result in downregulation of the transcript PU.1, which is crucial for normal myeloid differentiation. However the Sfpi1 gene mutations in AMLs are mainly point mutations. The C:G to T:A transitions which are the majority of them arise as a result of spontaneous mutations. Therefore, considering the effect of radiation for probability of the spontaneous mutations are required except the deletion of chromosome 2 to estimate AML risks induced by radiation. As spontaneous mutations occur in low probability with every cells divide, it is important that dynamics of hematopoiesis and effects of the dynamics changes with radiation are examined. In this study we use parameters which are obtained from experimental data using X-irradiated C3H/HeN mice to produce a mathematical model for calculating the dynamics of hematopoiesis. We focus the probability of spontaneous mutations of Sfpi1 gene and compare with the simulated AML risks in mice and experimental data.
