APOPTOSIS AND PERTURBATION OF CELL-CYCLE PROGRESSION IN AN ACIDIC ENVIRONMENT AFTER HYPERTHERMIA

The effects of an acidic environment on the induction of apoptosis by 42 degrees C hyperthermia were investigated hn acidic environment (pH 6.6) enhanced the hyperthermia-induced apoptosis in HL-60 human promye locytic leukemia cells as judged by the DNA fragmentation, flow cytome tric analysis of DNA content, and cleavage of poly(ADP-ribose) polymer ase. Hyperthermia exerted no effect on the expression of Bcl-2 and Bax , regardless of the environmental acidity during heating. The time of increase in apoptosis after heating coincided with the time of decreas e in the G(1)-phase cell population. It seemed that the increase in he at-induced apoptosis in HL-60 cells in an acidic environment mas due t o a direct increase in the proteolytic cleavage of poly(ADP-ribose) po lymerase by acidic caspases without the involvement of Bcl-2 and Bar, and that heat-induced apoptosis occurred during G(1) phase in HL-60 ce lls.