Cell Cycle Alteration, Apoptosis and
Response of Leukemic Cell Lines to Gamma Radiation with High- and Low-Dose
Rate
J. VÁVROVÁ1, M. ŘEZÁČOVÁ2, D. VOKURKOVÁ3,
J. PSUTKA4
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
Summary
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
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