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


CONCLUSIONS
Hyperthermia treatment is more effective at inducing apoptosis than radiation is in tumors that contain a population of low pH adapted cells.
Ohtsubo
T
T
Department of Otorhinolaryngology, Fukui Medical University, Matsuoka, Fukui, Japan. otsubo@fmsrsa.fukui-med.ac.jp
Igawa
H
H
Saito
T
T
Matsumoto
H
H
Park
H J
HJ
Song
C W
CW
Kano
E
E
Saito
H
H
D017209:Apoptosis / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology*; D003131:Combined Modality Therapy; D003470:Culture Media / Q000737:chemistry; D053938:DNA Fragmentation; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D008441:Maxillary Neoplasms / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D009363:Neoplasm Proteins / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011853:Radiobiology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000528:radiation effects
D003470:Culture Media; D009363:Neoplasm Proteins; D011065:Poly(ADP-ribose) Polymerases