A Biomathematical Model of Lymphopoiesis and its Application
to Acute and Chronic Irradiation Assessment
1
Hu ,
2
Cucinotta
Shaowen
Francis A.
1USRA, Space Life Sciences Division, Houston TX, USA, 2NASA, Lyndon B. Johnson Space Center, Houston TX, USA
Abstract
Objective. After the events of September 11, 2001,
there is an increasing concern of the occurrence of
radiological terrorism that may result in significant
casualties in densely populated areas. Much effort has
been made to establish various biomarkers to rapidly
assess radiation dose in mass-casualty and populationmonitoring scenarios, which are demanded for effective
medical management and treatment of the exposed
victims. Among these the count of lymphocytes in
peripheral blood and their depletion kinetics are the
most important early indicators of the severity of the
radiation injury. In this study, we examine a
biomathematical model of lymphopoiesis which can be
used as biodosimetric tool.
Results. With revised parameters for humans, we find
this model can reproduce several sets of clinical
lymphocyte data of accident victims over a wide range
of absorbed doses. In addition, the absolute
lymphocyte counts and the depletion rate constants
calculated by this model also show good correlation
with the Guskova formula and the Goans’ method. The
model can also generate consistent results with the
hematological data of the Techa River residents which
were exposed to chronic low-dose irradiation during
1950-1956.
Conclusions. This model can serve as a
computational tool in management of radiation accident
such as the nuclear crisis in Japan 2011, military
operations involving nuclear warfare, radiation therapy
protocol design, and space radiation risk assessment.
Model of Lymphopoiesis
Comparison with Goans’ Method
Three compartments:
X1: dividing precursor cells
X2: non-dividing maturing cells
X3: mature blood cells
Feed-back regulator I : dependent on the
concentration of X1, X2, and X3 cells
Model equations:
Comparison of model output and patient data
in Tokai-mura accident.
Modeling the Chernobyl Data
Model simulations of the whole course of
lymphocyte kinetics of patient C. The
simulation with an elevated division rate
shows a faster recovery.
Comparison with Baranov’s
Formula
Radiation and Hematopoiesis
Rapidly dividing, undifferntiated cells in tissue
such as hematopoietic stem cells and
gastrointestinal epithelium cells are the most
sensitive to radiation effects.
The hematopoiesis system can maintain a
constant level of the different blood cell types if
not seriously damaged.
Modeling the Tokai-mura Data
Comparison of model output and the reported
data of Chernobyl patient 97 (a), 48 (b), and
39(c). Lymphocyte data are reproduced from
UNSCEAR 1988 report.
(a) Biphasic dynamics of early lymphocyte
depletion depicted by model simulations for a
case with 6.0 Gy acute exposure. (b)
Lymphocyte
depletion
rate
constants
calculated from model simulations.
Modeling the Effects of Chronic
Irradiation
Baranov’s
formula
http://www.rem
m.nlm.gov/
Steady state of lymphocyte counts at the end
of chronic irradiation (1950–1956) for
inhabitants of the Techa River.
(a)
Hematopoietic
cell renewal systems
(E=Erythropoiesis,
G=Granulopoiesis,
Meg=Megakaryocytopoiesis)
(b)
Comparison of model output and data of 82
patients (8 groups) exposed to non-lethal
doses (a) and to lethal doses (b) in Chernobyl
accident.
Comparison of
model
outputs
(dash lines) of 5
doses and the
results
(lines
with symbols) of
Guskova’s
method.
Model simulations of the depression
lymphocytes at different dose rates.
of