Physiol. Res. 53: 335-342, 2004

Cell Cycle Alteration, Apoptosis and Response of Leukemic Cell Lines to Gamma Radiation with High- and Low-Dose Rate


1Institute of Radiobiology and Immunology, Purkyně Military Medical Academy, Hradec Králové, 2Department of Medical Biochemistry, Faculty of Medicine Hradec Králové, Charles University Prague, 3Institute of Clinical Immunology and Allergology, University Hospital, Hradec Králové, 4Department of Military Medical Service Organization, Purkyně Military Medical Academy, Hradec Králové, Czech Republic

Received April 29, 2003
Accepted July 15, 2003

The aim of this work was to compare the effect of gamma radiation with sub-low dose-rate 1.8 mGy/min (SLDR), low dose-rate 3.9 mGy/min (LDR) and high dose-rate 0.6 Gy/min (HDR) on human leukemic cell lines with differing p53 status (HL-60, p53 deficient and MOLT-4, p53 wild) and to elucidate the importance of G2/M phase cell cycle arrest during irradiation. Radiosensitivity of HL-60 and MOLT-4 cells was determined by test of clonogenity. Decrease of dose-rate had no effect on radiosensitivity of MOLT-4 cells (D0 for HDR 0.87 Gy, for LDR 0.78 Gy and for SLDR 0.70 Gy). In contrast, a significant increase of radioresistance after LDR irradiation was observed for p53 negative HL-60 cells (D0 for HDR 2.20 Gy and for LDR 3.74 Gy). After an additional decrease of dose-rate (SLDR) D0 value (2.92 Gy) was not significantly different from HDR irradiation. Considering the fact that during HDR the cells are irradiated in all phases of the cell cycle and during LDR mainly in the G2 phase, we have been unable to prove that the G2 phase is the most radiosensitive phase of the cell cycle of HL-60 cells. On the contrary, irradiation of cells in this phase induced damage reparation and increased radioresistance. When the dose-rate was lowered, approximately to 1.8 mGy/min, an opposite effect was detected, i.e. D0 value decreased to 2.9 Gy. We have proved that during SLDR at first (dose up to 2.5 Gy) the cells accumulated in G2 phase, but then they entered mitosis or, if the cell damage was not sufficiently repaired, the cells entered apoptosis. The entry into mitosis has a radiosensibilizing effect.

Key words
Leukemia cell line • Ionizing radiation • Apoptosis • G2 arrest


© 2004 by the Institute of Physiology, Czech Academy of Sciences