Acidic environment modifies heat- or radiation-induced apoptosis in human maxillary cancer cells

Abstract

Purpose: The effects of hyperthermia or irradiation on cell killing and induction of apoptosis were evaluated using human maxillary carcinoma IMC-3 cells and low pH (pH 6.8) adapted cells (IMC-3-pH). Methods and Materials: Cellular heat-sensitivity or radiosensitivity was determined using the clonogenic assay. Apoptosis was assessed on the basis of a flow cytometric determination of the DNA content, DNA fragmentation, and poly(ADP-ribose)polymerase cleavage. Results: When IMC-3 cells or IMC-3-pH cells were exposed to heat at 44°C in pH 6.8 medium, an increase in thermosensitivity was observed compared with when the IMC-3 cells were exposed to heat at 44°C in pH 7.4 medium. However, the selective reduction in survival was not observed after irradiation. In IMC-3 cells, apoptosis after heating at 44°C for 60 min in pH 7.4 medium occurred earlier than that after 8 Gy irradiation, although both thermal and irradiated doses decreased the cell count to 10%. The degree of apoptosis after heating at pH 6.8 in IMC-3 cells or IMC-3-pH cells was greater than that at pH 7.4 in IMC-3 cells. However, the degree of apoptosis after 8 Gy irradiation at pH 6.8 in IMC-3 cells or IMC-3-pH cells was smaller than that at pH 7.4 in IMC-3 cells. Conclusion: Hyperthermia treatment is more effective at inducing apoptosis than radiation is in tumors that contain a population of low pH adapted cells.