Home General Physiology and Biophysics 2010 General Physiology and Biophysics Vol.29, No.3, p.275–281, 2010

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General Physiology and Biophysics Vol.29, No.3, p.275–281, 2010

Title: Exposure to fractionated dose of 60 Gy affects molecular response of HL-60 cells to irradiation
Author: Jiřina Vávrová, Aleš Tichý, Martina Řezáčová, Lenka Zárybnická, Zuzana Šinkorová and Jan Österreicher

Abstract: In this work we evaluated changes in molecular response of human promyelocyte leukemia cells HL-60 and HL-60-IR cells (HL-60 irradiated by 10 cycles of radiation with total dose of 60 Gy, given over a period of 3 months) to irradiation by the dose of 2 and 8 Gy. Analysis of CD11b and apoptosis by flow-cytometry revealed that on 3rd day after irradiation by 8 Gy the HL-60-IR are more resistant to radiation-induced apoptosis and more differentiated (increase in CD11b in non-apoptotic cells) than regular HL-60.
We found that both types of cells have high basal level of phosphorylated extracellular signal-regulated kinases Erk1/2 . Irradiation induces decrease in Erk1/2 phosphorylation after 4 and 8 h in both cell types. However, in HL-60-IR cells Erk1/2 phosphorylation is restored faster than in HL-60. Also it was found that in contrary to HL-60 cells, the HL-60-IR cells react to 2 Gy irradiation by p53 independent increase in p21(WAF1/Cip1), and not by activation of checkpoint kinase Chk-2.
Therefore we concluded that relatively high dose of radiation (6 Gy) does not lead after 10 repetitive irradiations to eradication of HL-60 cells, but instead increases their radioresistance, increases the ability to differentiate, alters MAPK response, increases amount of p21(WAF1/Cip1), and decreases induction of apoptosis by ionizing radiation. p21(WAF1/Cip1) might prevent apoptosis induction and trigger permanent cell-cycle arrest, which can also contribute to regression of this leukaemia after therapy.

Keywords: Ionizing radiation — Radioresistance — p21(WAF1/Cip1) — Erk1/2 — Apoptosis
Year: 2010, Volume: 29, Issue: 3 Page From: 275, Page To: 281
doi:10.4149/gpb_2010_03_275


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