Hematopoietic cell renewal systems: mechanisms of coping and failing after chronic exposure to ionizing radiation |
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Authors: | Theodor M Fliedner Dieter H Graessle |
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Institution: | (1) Radiation Medicine Research Group and WHO Liaison Institute for Radiation Accident Management, Faculty of Medicine, University of Ulm, Helmholtzstrasse 20, 89081 Ulm, Germany |
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Abstract: | On the occasion of the first international workshop on systems radiation biology we review the role of cell renewal systems
in maintaining the integrity of the mammalian organism after irradiation. First, 11 radiation emergencies characterized by
chronic or protracted exposure of the human beings to ionizing irradiation were “revisited”. The data provide evidence to
suggest that at a daily exposure of about 10–100 mSv, humans are capable of coping with the excess cell loss for weeks or
even many months without hematopoietic organ failure. Below 10 mSv/day, the organisms show some cellular or subcellular indicators
of response. At dose rates above 100 mSv/day, a progressive shortening of the life span of the irradiated organism is observed.
To elucidate the mechanisms relevant to tolerance or failure, the Megakaryocyte–thrombocyte cell renewal system was investigated.
A biomathematical model of this system was developed to simulate the development of thrombocyte concentration as a function
of time after onset of chronic radiation exposure. The hematological data were taken from experimental chronic irradiation
studies with dogs at the Argonne National Laboratory, USA. The results of thrombocyte response patterns are compatible with
the notion of an “excess cell loss” (compared to the steady-state) in all proliferative cell compartments, including the stem
cell pool. The “excess cell loss” is a function of the daily irradiation dose rate. Once the stem cell pool is approaching
an exhaustion level, a “turbulence region” is reached. Then it takes a very little additional stress for the system to fail.
We conclude that in mammalian radiation biology (including radiation medicine), it is important to understand the physiology
and pathophysiology of cell renewal systems in order to allow predicting the development of radiation induced lesions. |
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