Modeling study of radiation effects on thrombocytopoietic and granulocytopoietic systems in humans

Biologically motivated mathematical models, which describe the dynamics of thrombocytopoiesis and granulocytopoiesis in nonirradiated and irradiated humans, are developed. These models, being based on conventional biological theories, are implemented as the systems of nonlinear differential equations whose variables and constant parameters have clear biological meaning. Thorough analytical and numerical analysis of the proposed models is performed. It is found that the models on hand are capable of reproducing the dynamical regimes which are typical for the thrombocytopoiesis and granulocytopoiesis in the norm and in the case of hematological disorders, such as cyclic thrombocytopenia and cyclic neutropenia. The elaborated models are applied to investigate the dynamics of thrombocytopoiesis and granulocytopoiesis in astronauts exposed to space radiation during long-term missions such as voyages to Mars. The dose rate equivalent for space radiation (galactic cosmic rays (GCR) and solar particles event (SPE)) is taken as a variable parameter of the models. It is revealed that the thrombocytopoietic and granulocytopoietic systems can adapt themselves to GCR exposure. It is also shown that an SPE causes damped oscillations of the “effective” radiosensitivity of these cell systems that, in turn, determines the strength of their responses to the subsequent SPE. Specifically, depending on the time interval between SPEs, the preceding SPE can induce either radiosensitization or radioprotection effects on the thrombocytopoietic and granulocytopoietic systems. In the last case, adaptive responses to the subsequent SPE in these systems occur. All this testifies to the efficiency of employment of the developed models in investigation and prediction of effects of space radiation on the thrombocytopoietic and granulocytopoietic systems. The developed models of these vital body systems provide a better understanding of the risks to health from the solar particles events and enable one to evaluate the need of operational applications of countermeasures for astronauts in the long-term space missions.