Stem Cells, Vol 12, 506-513, Copyright © 1994 by AlphaMed Press
Erythropoietin increases the radioresistance of a clonal hematopoietic progenitor cell line expressing a transgene for the erythropoietin receptor
MA Santucci, JH Pierce, S Zannini, A Fortuna, G Frezza, L Babini, MM Rosenstein and JS Greenberger
Istituto di Cancerologia, Universita di Bologna Medical School, Italy.
Erythropoietin (Epo) is a serum glycoprotein growth factor required for the
survival, proliferation and differentiation of committed erythroid
progenitor cells. In the present study, we sought to determine whether the
action of Epo via its receptor is also implicated in the repair of
radiation-induced cell damage. Overexpression of the Epo receptor (Epo- R)
was achieved as a result of transfection of the 32D cl 3 clonal
hematopoietic cell line. These clonal lines allowed us to investigate the
effects of Epo on the radiation sensitivity in vitro of a clonal murine
hematopoietic progenitor cell line. Low level expression of Epo- R on many
hematopoietic cell types was thus circumvented. Ligand binding of Epo
resulted in increased radioresistance of 32D cl 3 subclonal lines
expressing the Epo-R transgene. The D0 of 32D Epo-R cells at 1.49 Gy/min
was 1.33 Gy and n was 1.39. The D0 of parental clonal cell line 32D cl 3
cells at 1.49 Gy/min was 1.36 Gy and n was 1.39. In contrast, at the low
dose rate of 0.0595 Gy/min, the D0 of 32D Epo-R cells was 2.0 Gy and n was
1.24, while parental clonal line 32D cl 3 showed a D0 of 1.35 Gy and n was
1.39. The increased radioresistance was statistically significant at low
dose rate (p < 0.05). Combined exposure to Epo and interleukin 3 (IL-3)
increased proliferation of 32D Epo-R cells but did not induce a detectable
further increase in radioresistance. Temporal dissociation between growth
factor-activated tyrosine phosphorylation of intracellular substrates, and
the radioprotective effect was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
