Radiation-enhanced differentiation of erythroid progenitor cells and its relation to reproductive cell death

Abstract

Terminally differentiated cells usually do not divide and are, thus, reproductively dead. To elucidate the significance of radiation-enhanced differentiation to reproductive cell death, murine erythroid progenitor cells were gamma-irradiated in plasma clot cultures and the development of haemoglobinized clones was studied thereafter. If irradiation occurred when the cells had resumed proliferation, the total numbers of haemoglobinized clones and, in parallel, the numbers of newly haemoglobinized clones were elevated above control levels 6-24 h after 10-30 Gy and 24-48 h after 1 Gy respectively. Thereafter, clone numbers decreased below controls. This decrease was faster with the newly haemoglobinized clones, indicating that both the accumulation of haemoglobinized clones and fast exhaustion of the pool of more primitive precursors in the cultures are due to accelerated differentiation. The haemoglobinized clones appearing after irradiation were reduced in size without indication of direct cell death. We conclude that the reproductive cell death occurring in our system is due to enhancement of differentiation. Enhancement of differentiation is expressed by omission of cell cycles normally passed through by the cell progeny before terminal differentiation is reached. Dependence of differentiation enhancement on the presence of cycling cells at the time of irradiation indicates involvement of growth of essential cytoplasmic constituents during mitotic delay as observed in other cell systems.

The effects of low dose X-irradiation on osteoblastic MC3T3-E1 cells in vitro

“…Interestingly, irradiation also induced terminal differentiation in some other culture systems, such as, human skin fibroblasts [47] and erythroid progenitor cells [48]. While some reported ionizing radiation greater than 2 Gy promoted osteoblasts terminal differentiation [18,23].…”

A Mechanism of Intracellular Timing and its Cooperation with Extracellular Signals in Controlling Cell Proliferation and Differentiation, an Amended Hypothesis

“…The relevance of this principle is indicated by the fact that in a number of tumor types cell cycle arrest and end-stage di!erentiation can be induced by treatment with agents that increase the cytoplasmic/nuclear ratio (von Wangenheim et al, 1995;Schwenke et al, 1996).…”

The role of cell differentiation in controlling cell multiplication and cancer

“…That is, in accordance with the number of cell cycles to be passed through before hemoglobin synthesis can be initiated by EPO, small colonies of erythrocytes from the more mature progenitors (CFU-E) appear early after plating, whereas the progeny of the most immature progenitors (BFU-E), with 5-10 ampliWcation divisions left to be passed through, appear as large hemoglobinized burst like colonies 5-8 days later (Schwenke et al 1996). Thus, the erythroid precursors must time on their own when to change their response to EPO and to start hemoglobin Fig.…”

“…Thus, the amount of cytoplasm per genome is elevated with the consequences depicted in Fig. 2a: Depending on the radiation dose and, thus, the extent of excess cytoplasmic growth, a few or even all of the cell cycles are skipped that were originally programmed to be passed through prior to terminal diVerentiation (Schwenke et al , 1996von Wangenheim 1975;von Wangenheim and Howard 1978).…”