Park, H.J., Lyons, J.C., Griffin, R.J., Limm, B.U. and Song, C.W. Apoptosis and Cell Cycle Progression in an Acidic Environment after Irradiation.

Apoptosis and cell cycle progression in HL60 cells irradiated in an acidic environment were investigated. Apoptosis was determined by TUNEL staining, PARP cleavage, DNA fragmentation, and flow cytometry. The majority of the apoptosis that occurred in HL60 cells after 4 Gy irradiation took place after G₂/M-phase arrest. When irradiated with 12 Gy, a fraction of the cells underwent apoptosis in G₁ and S phases while the rest of the cells underwent apoptosis in G₂/M phase. The apoptosis caused by 4 and 12 Gy irradiation was transiently suppressed in medium at pH 7.1 or lower. An acidic environment was found to perturb progression of irradiated cells through the cell cycle, including progression through G₂/M phase. Thus it was concluded that the suppression of apoptosis in the cells after 4–12 Gy irradiation in acidic medium was due at least in part to a delay in cell cycle progression, particularly the prolongation of G₂/M-phase arrest. Irradiation with 20 Gy indiscriminately caused apoptosis in all cell cycle phases, i.e. G₁, S and G₂/M phases, rapidly in neutral pH medium and relatively slowly in acidic pH medium. The delay in apoptosis in acidic medium after 20 Gy irradiation appeared to result from mechanisms other than prolonged G₂/M-phase arrest.