Comparative Modeling Analysis of the Hematopoiesis Dynamics in Mammals Exposed to Nonuniform and Uniform Acute Irradiation.

Abstract

Biologically motivated mathematical models of the dynamics of the major hematopoietic lineages (the thrombopoietic, erythropoietic, granulopoietic, and lymphopoietic systems) in mammals (rodents) exposed to nonuniform acute irradiation are developed and thoroughly investigated. These models are based on earlier developed mathematical models, which are capable of predicting the dynamics of these systems in mammals (rodents) exposed to uniform acute/chronic irradiation. The developed models are the systems of nonlinear ordinary differential equations whose variables and constant parameters have clear biological meaning. It is found that these models are capable of reproducing a lesser depletion of the major hematopoietic lineages and faster recovery in rodents (rats, mice) after nonuniform acute irradiation than those after uniform acute irradiation at equal whole-body doses of such exposures. The nature of this phenomenon is elucidated in the framework of the models. Thorough comparative analysis of effects of nonuniform (partial) and uniform acute irradiation on the major hematopoietic lineages is performed. It is revealed that the lymphopoietic system is the most susceptible major hematopoietic lineage both to uniform and nonuniform (partial) acute irradiation. It is argued that the first-day level of the concentration of functional blood cells in this system (blood lymphocytes) after nonuniform (partial) acute irradiation can serve for early assessment of the risk of acute radiation syndrome. It is also shown that the modeling results on the first-day levels of the blood lymphocyte concentration after various partial acute exposures are in a very good agreement with the relevant experimental data. This agreement testifies to the applicability of the developed model of the lymphopoietic system to be used in the prognostic aims; in particular, for predicting the development of lymphocytopenia after partial acute irradiation. The modeling results imply that the prognostic use of a whole-body dose of nonuniform acute irradiation is not effective. The obtained results testify to the efficiency of the proposed dynamic modeling approach in the study of the effects of nonuniform acute irradiation on the major hematopoietic lineages and the validity of using developed models of the major hematopoietic lineages in the prediction of the effects of nonuniform acute irradiation on these systems in rodents and, after appropriate modification of the models, in humans.