Acidic Environment Modifies Heat- Or Radiation-Induced Apoptosis in Human Maxillary Cancer Cells

Int J Radiat Oncol Biol Phys. 2001 Apr 1;49(5):1391-8. doi: 10.1016/s0360-3016(00)01590-x.


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 degrees 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 degrees 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 degrees 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology*
  • Cell Division / physiology
  • Cell Survival / physiology*
  • Combined Modality Therapy
  • Culture Media / chemistry
  • DNA Fragmentation
  • Humans
  • Hydrogen-Ion Concentration*
  • Hyperthermia, Induced*
  • Maxillary Neoplasms / metabolism
  • Maxillary Neoplasms / physiopathology*
  • Maxillary Neoplasms / therapy
  • Neoplasm Proteins / metabolism
  • Poly(ADP-ribose) Polymerases / metabolism
  • Radiobiology
  • Time Factors
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / radiation effects


  • Culture Media
  • Neoplasm Proteins
  • Poly(ADP-ribose) Polymerases