Abstract
A low-dose risk is a controversial issue because there are gaps between epidemiology and biology. Cancer is thought to be induced through multi-mutational steps. Some biologically-based models can well describe the age pattern of the cancer incidence among the atomic bomb survivors. However, the role of radiation in carcinogenesis is unclear since model-fitting to data shows a good result but the meanings of biological parameters are different among the models. Recent progress in leukemia research provides a useful information to mathematical modeling. We will present the model for radiation-induced leukemia in support of our "cell kinetics disturbance hypothesis". Note that previous initiation theory of radiation does not have a supportive biological evidence and the spontaneous translocation specific to ALL occur much more frequency than radiation-induced translocation. Moreover, the first step of carcinogenesis during fetus is likely to occur irrespective of radiation exposure. We suggested that asymmetric division of stem cells supply mature cells and genomic instability induces delayed cell death. The difference in cellular kinetics between mutated and non-mutated stem cells results in clonal expansion of the mutated cells due to their growth advantage. Consequently, risk assessment for carcinogenesis should be based on extrapolation from the dose response relationship of cellular kinetics of stem cell population.
