Early hematopoiesis inhibition under chronic radiation exposure in humans

Abstract

The major goal of this study was to identify and quantitatively describe the association between the characteristics of chronic (low-dose rate) exposure to (low LET) ionizing radiation and cellularity of peripheral blood cell lines. About 3,200 hemograms (i.e., spectra of blood counts) obtained over the years of maximal exposure to ionizing radiation (1950)(1951)(1952)(1953)(1954)(1955)(1956)) for inhabitants of the Techa River were used in analyses. The mean cumulative red bone marrow dose (with standard errors), calculated using Techa River Dosimetry System-2000, was 333.6 ± 4.6 mGy (SD = 259.9 mGy, max = 1151 mGy) to the year 1956. The statistical approach included both empirical methods for estimating frequencies of cytopenic states of the investigated blood cell lines (e.g. neutrophile, platelets, erythrocyte, etc.), and regression methods, including generalized linear models and logistic regressions which allowed taking into account confounding factors (e.g., attained age, age at maximal exposure, presence of concomitant diseases, and demographic characteristics). The results of the analyses demonstrated hematopoiesis inhibition manifested by a decrease in peripheral blood cellularity and an increase in the frequency of cytopenia in all blood cell lines (leukocytes, including lymphocytes, monocytes, neutrophiles, as well as platelets and erythrocytes). The intensity of hematopoiesis inhibition in the period of maximal exposures is determined by the combined influence of the dose rate and cumulative dose. The contribution of specific confounding factors was quantified and shown to be much less important than dose characteristics. The best predictor among dose characteristics was identified for each blood cell line. A 2-fold increase in dose rate is assumed to be a characteristic of radiosensitivity and a quantitative characteristic of the effect.

Impacts of Terrestrial Ionizing Radiation on the Hematopoietic System

“…Hence, the insufficiency of white blood cells is followed by a shortfall of platelets and red blood cells. Further, the shortage of white blood cells can trigger infections and the shortage of platelets can cause uncontrolled bleeding from body tissues [71,72].…”

Modeling hematopoietic system response caused by chronic exposure to ionizing radiation

“…Recently Akleyev et al (2010) presented new results on the hematopoiesis inhibition. In that paper we identified and quantitatively described the association between some characteristics of chronic (low dose-rate) exposure to (low-LET) IR and cellularity of peripheral blood cell lines.…”

“…The data analysis applied in Akleyev et al (2010) was based on traditional empirical and regression methods, and the model presented to explain the obtained results was statistically based. However, it may also be interesting to investigate how the results obtained can be interpreted in terms of some biologically-motivated model of hematopoiesis for individuals chronically exposed to low and intermediate doses of IR.…”

“…However, it may also be interesting to investigate how the results obtained can be interpreted in terms of some biologically-motivated model of hematopoiesis for individuals chronically exposed to low and intermediate doses of IR. One conclusion from the study of Akleyev et al (2010) was that the contribution of specific confounding factors reflecting individual variability in response patterns was quantified and shown to be much less important than dose characteristics. This is in accordance with the well-known property of IR-induced effects that the primary inhibition response to IR (at least for high-dose acute exposure to IR) is largely a deterministic process (ICRP, 1991), i.e., that the process is predetermined by radiation dose and, to a much lesser extent, by individual heterogeneity.…”

“…The dynamics of all compartments are linked in this model. This remarkable property of the model allows for simultaneous analysis of the effects in different blood lines; therefore, this property was determinative in selecting the basic approach for further generalization and applying it on the results of Akleyev et al (2010). The model is elaborated in detail especially with respect to i) evaluating model parameters by using available data, ii) uncovering many useful properties of the model by methods of nonlinear dynamics, and iii) explaining and quantitatively describing the cyclic phenomena in hematopoiesis, such as cyclical neutropenia and chronic myelogenous leukemia.…”