Radiation Sensitivities in the Terminal Stages of Megakaryocytic Maturation and Platelet Production

Abstract

These studies examined the effects of X radiation and interleukin 3 (IL-3), which is an effective cytokine for the generation of megakaryocytopoiesis from X-irradiated hematopoietic stem/progenitor cells, on the terminal process of human megakaryocytopoiesis and thrombopoiesis. Mature megakaryocytes were induced by culturing CD34(+) cells from normal human peripheral blood in a serum-free liquid culture stimulated with thrombopoietin. The experiments contained the following groups: control cultures with nonirradiated cells incubated for 15 days; cultures treated with IL-3 on day 7 or day 11, cultures irradiated with 2 Gy on day 7 or day 11, and cultures treated with IL-3 immediately after X irradiation. The nonirradiated control cultures produced megakaryocytes from day 7, and both the megakaryocyte and platelet generation reached a peak on day 12-13. When X irradiation was performed on day 7, both the megakaryocyte and platelet numbers decreased remarkably, while no significant effect was observed on those numbers when cultures were X-irradiated on day 11. IL-3 showed neither protective nor promoting effects on the terminal stages of megakaryocytic maturation and platelet production. The results demonstrated that mature megakaryocytes are radiosensitive but that the radiosensitivity decreased with the terminal stages of megakaryocytic maturation, especially for the megakaryocytes entering into proplatelet formation.

Predictive factors of cytotoxic damage in radioactive iodine treatment of differentiated thyroid cancer patients

“…The absorbed dose rate in the air on the neck surface was measured using a γ-radiation survey meter in patients administered 3.7 (white circles) and 5.5 GBq (black circles) for 4 days following administration. are radiosensitive; however, the sensitivity was observed to decrease at the terminal stages of megakaryocytic maturation, particularly as the megakaryocytes entered the proplatelet formation stage (22). Thus, it is suggested that the reduction of PLT on day 30 observed in the present study is attributed to the effect of radiation on the megakaryocytic maturation system.…”

Development and Licensure of Medical Countermeasures for Platelet Regeneration after Radiation Exposure

“…After irradiation, megakaryocytes, which give rise to platelets, migrate to the osteoblastic niche (4). Megakaryocytes in the circulation are known to be more radioresistant to radiation than other bone marrowderived cells; however, their progenitor populations appear to be more radiosensitive (5). Depending on the degree of radiation damage, a drop in platelet count can be observed in less than a week (6), with the risk of life-threatening bleeding increased as the level of circulating platelets drops below 20,000/mm 3 .…”

Mathematical model of radiation effects on thrombopoiesis in rhesus macaques and humans

“…MK radiosensitivity was engineered into the model as the hypothesized cause for the elimination of the plateau phase at higher doses. The inclusion of MK radiosensitivity is supported by experimental in vitro data in human cells (Monzen et al, 2009). However, further experiments are warranted to both validate this proposed mechanism and explain the differences in MK radiosensitivity across species.…”