Analysis of a hormesis effect in the leukemia-caused mortality among atomic bomb survivors

Yakovlev and Polig (1996) developed a mechanistically motivated stochastic model of radiation carcinogenesis allowing for cell death. The key feature of the model is that it allows for radiation-induced cell killing to compet e with the process of tumor promotion. This model describes and explains a wide range of experimental findings documented in the radiobiological liter ature, including the inverse dose-rate effect and radiation hormesis. The m odel has successfully been applied to various sets of experimental and epid emiological data to gain quantitative insight into the processes of tumorig enesis induced by radiation and chemical carcinogens. In this paper, we dis cuss the most recent application of the Yakovlev-Polig model to the analysi s of epidemiological data on the mortality caused by radiation-induced leuk emia (all types) among the atomic bomb survivors (Hiroshima and Nagasaki). Nonparametric estimates of the hazard function for leukemia latency time we re obtained for three different dose groups identified in the Hiroshima coh ort. The behavior of these estimates suggests the presence of the hormesis- type effect in relation to leukemia-caused mortality. A parsimonious versio n of the mechanistic model yields parametric estimates that are in good agr eement with their nonparametric counterparts. Using the parametric model, w e corroborated the presence of a moderate hormesis effect in the Hiroshima data. However, we have been unable to uncover the same effect with the Naga saki cohort of the atomic bomb survivors.