Modeling deterministic effects in hematopoietic system caused by chronic exposure to ionizing radiation in large human cohorts.
Abstract
A new model of the hematopoietic system for humans chronically exposed to ionizing
radiation allows for quantitative description of the initial hematopoiesis inhibition
and subsequent increase in the risks of late stochastic effects such as leukemia.
This model describes the dynamics of the hematopoietic stem cell compartment as well
as the dynamics of each of the three blood cell types (leukocytes, erythrocytes, and
platelets). The model parameters are estimated from the results of other experiments.
They include the steady-state numbers of hematopoietic stem cells and peripheral blood
cell lines for an unexposed organism, amplification parameters for each blood cell
line, parameters describing the proliferation and apoptosis, parameters of feedback
functions regulating the steady-state numbers, and characteristics of radiosensitivity
in respect to cell death and non-lethal cell damages. The dynamic model of hematopoiesis
is applied to the data on a subcohort of the Techa River residents with hematological
measurements (e.g., blood counts) performed in 1950-1956 (which totals to about 3,500
exposed individuals). Among well-described effects observed in these data are the
slope values of the dose-effect curves describing the hematopoietic inhibition and
the dose rate patterns of the fractions of cytopenic states (e.g., leukopenia, thrombocytopenia).
The model has been further generalized by inclusion of the component describing the
risk of late stochastic effects. The risks of the development of late effects (such
as leukemia) in population groups with specific patterns of early reactions in hematopoiesis
(such as leukopenia induced by ionizing radiation) are investigated using simulation
studies and compared to data.
Type
Journal articleSubject
ApoptosisBlood Cell Count
Blood Platelets
Cell Differentiation
Cell Proliferation
Cohort Studies
Environmental Exposure
Erythrocytes
Hematopoietic System
Humans
Leukocytes
Models, Biological
Mutagenesis
Population Groups
Radiation, Ionizing
Stochastic Processes
Time Factors
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https://hdl.handle.net/10161/14859Published Version (Please cite this version)
10.1097/HP.0b013e3181c61dc1Publication Info
Akushevich, Igor V; Veremeyeva, Galina A; Dimov, Georgy P; Ukraintseva, Svetlana V;
Arbeev, Konstantin G; Akleyev, Alexander V; & Yashin, Anatoly I (2010). Modeling deterministic effects in hematopoietic system caused by chronic exposure
to ionizing radiation in large human cohorts. Health Phys, 99(3). pp. 322-329. 10.1097/HP.0b013e3181c61dc1. Retrieved from https://hdl.handle.net/10161/14859.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Igor Akushevich
Research Professor in the Social Science Research Institute
Konstantin Arbeev
Associate Research Professor in the Social Science Research Institute
Konstantin G. Arbeev received the M.S. degree in Applied Mathematics from Moscow State
University (branch in Ulyanovsk, Russia) in 1995 and the Ph.D. degree in Mathematics
and Physics (specialization in Theoretical Foundations of Mathematical Modeling, Numerical
Methods and Programming) from Ulyanovsk State University (Russia) in 1999. He was
a post-doctoral fellow in Max Planck Institute for Demographic Research in Rostock
(Germany) before moving to Duke University in 2004 to work as a Resea
Svetlana Ukraintseva
Research Professor in the Social Science Research Institute
Dr. Ukraintseva studies causes of human aging and related decline in resilience, to
identify genetic and other factors responsible for the increase in mortality risk
with age eventually limiting longevity. She explores complex relationships, including
trade-offs, between physiological aging-changes and risks of major diseases (with
emphasis on Alzheimer’s and cancer), as well as survival, to find new genetic and
other targets for anti-aging interventions and disease prevention. S
Anatoli I. Yashin
Research Professor in the Social Science Research Institute
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