Modeling hematopoietic system response caused by chronic exposure to ionizing radiation.
A new model of the hematopoietic system response in humans chronically exposed to ionizing radiation describes the dynamics of the hematopoietic stem cell compartment as well as the dynamics of each of the four blood cell types (lymphocytes, neutrophiles, erythrocytes, and platelets). The required model parameters were estimated based on available results of human and experimental animal studies. They include the steady-state number of hematopoietic stem cells and peripheral blood cell lines in an unexposed organism, amplification parameters for each blood line, parameters describing proliferation and apoptosis, parameters of feedback functions regulating the steady-state numbers, and characteristics of radiosensitivity related to cell death and non-lethal cell damage. The model predictions were tested using data on hematological measurements (e.g., blood counts) performed in 1950-1956 in the Techa River residents chronically exposed to ionizing radiation since 1949. The suggested model of hematopoiesis is capable of describing experimental findings in the Techa River Cohort, including: (1) slopes of the dose-effect curves reflecting the inhibition of hematopoiesis due to chronic ionizing radiation, (2) delay in effect of chronic exposure and accumulated character of the effect, and (3) dose-rate patterns for different cytopenic states (e.g., leukopenia, thrombocytopenia).
Center for Population Health and Aging, Duke University, 002 Trent Hall, Box 90408, Durham, NC 27708-0408, USA. igor.akushevich@duke.edu
Igor V
IV
Akushevich
Galina A
GA
Veremeyeva
Georgy P
GP
Dimov
Svetlana V
SV
Ukraintseva
Konstantin G
KG
Arbeev
Alexander V
AV
Akleyev
Anatoly I
AI
Yashin
D001792:Blood Platelets / Q000528:radiation effects; D003198:Computer Simulation; D004307:Dose-Response Relationship, Radiation; D004912:Erythrocytes / Q000528:radiation effects; D005246:Feedback; D006410:Hematopoiesis / Q000528:radiation effects; D006412:Hematopoietic Stem Cells / Q000528:radiation effects; D006413:Hematopoietic System / Q000473:pathology* / Q000528:radiation effects*; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008954:Models, Biological; D009504:Neutrophils / Q000528:radiation effects; D011832:Radiation Injuries / Q000473:pathology*; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D013269:Stochastic Processes
Radiat Environ Biophys. 2008 Feb;47(1):63-9
18087709
PLoS One. 2007 Apr 04;2(4):e345
17406669
Wiley Interdiscip Rev Syst Biol Med. 2010 Mar-Apr;2(2):235-244
20836025
Stem Cells. 1995 May;13 Suppl 1:283-9
7488958
Cancer Biother Radiopharm. 2002 Aug;17(4):405-26
12396705
Health Phys. 2001 Oct;81(4):395-405
11569634
Mech Ageing Dev. 2003 Apr;124(4):433-43
12714250
Math Biosci. 2007 Aug;208(2):538-51
17300818
Radiat Environ Biophys. 2010 May;49(2):281-91
20340030
J Theor Biol. 2006 Sep 21;242(2):288-99
16603196
Health Phys. 2010 Sep;99(3):322-9
20699693
Health Phys. 2010 Sep;99(3):337-46
20699695
Theor Popul Biol. 2008 Feb;73(1):1-10
17977568
J Math Biol. 2009 Jan;58(1-2):285-322
18317766
Stem Cells. 1995 May;13 Suppl 1:290-300
7488959
Bull Math Biol. 2006 Nov;68(8):2321-51
17086497
Math Biosci. 2000 Sep;167(1):19-30
10942784
Health Phys. 2010 Feb;98(2):282-9
20065695
Radiat Res. 2005 Nov;164(5):591-601
16238436
Stem Cells. 1995 May;13 Suppl 1:268-75
7488956
Bull Math Biol. 2002 Sep;64(5):861-86
12391860
J Theor Biol. 2005 Nov 21;237(2):117-32
15975596
Ann ICRP. 1991;21(1-3):1-201
2053748
Theor Popul Biol. 1985 Apr;27(2):154-75
4023952
Exp Hematol. 2009 Apr;37(4):514-24
19216021