title: Exposure to fractionated dose of 60 Gy affects molecular response of HL-60 cells to irradiation.
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.
authors.affiliation: Department of Radiobiology, Faculty of Health Sciences, Hradec Králové, University of Defence Brno, Czech Republic. vavrova@pmfhk.cz
authors.forename: Jiřina
authors.initials: J
authors.lastname: Vávrová
authors.forename: Aleš
authors.initials: A
authors.lastname: Tichý
authors.forename: Martina
authors.initials: M
authors.lastname: Rezáčová
authors.forename: Lenka
authors.initials: L
authors.lastname: Zárybnická
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Sinkorová
authors.forename: Jan
authors.initials: J
authors.lastname: Osterreicher
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D002454:Cell Differentiation / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays / Q000627:therapeutic use; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology / Q000532:radiotherapy*; D020935:MAP Kinase Signaling System / Q000528:radiation effects*; D010766:Phosphorylation; D011836:Radiation Tolerance / Q000502:physiology*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21