Effects of Acute and Chronic Irradiation on Human Hematopoiesis

Abstract

Chapter 7 is devoted to the development and thorough study of the biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombopoietic, lymphopoietic, granulopoietic, and erythropoietic systems) in nonirradiated and acutely/chronically irradiated humans. These models are implemented as the systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is revealed that the developed models are capable of reproducing the homeostasis states in these systems in healthy humans, as well as the dynamical regimes, which are typical for patients with cyclic hematological disorders. It is shown that the model of the human lymphopoietic system is capable of simulating the dynamics of the blood lymphocytes in patients received allogenic stem cell transplantation. It is found that the developed models are capable of reproducing clinical data on the dynamics of the major hematopoietic lineages in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the ”lethal” dose rates of chronic irradiation evaluated within the models of the major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human major hematopoietic lineages to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the human major hematopoietic lineages for a vast pattern of irradiation scenarios. As an example, the developed models are applied to simulate the dynamics of the major hematopoietic lineages in astronauts in a typical spacecraft traveling in interplanetary space. The dose rate equivalent for space radiation [galactic cosmic rays (GCR) and solar particles events (SPE)] is taken as a variable parameter of the models. The obtained results convincingly demonstrate the efficiency of employment of the developed models in the investigation and prediction of the effects of space radiation on the human major hematopoietic lineages. Such modeling predictions could provide a better understanding of the risks to health from the space radiation environment and enable one to evaluate the need for operational applications of countermeasures for astronauts. Additionally, the developed models of the human major hematopoietic lineages could be employed to estimate the risks for the health of people exposed to acute/chronic irradiation due to environmental radiological events.