Hyperthermia induces apoptosis in malignant fibrous histiocytoma cells in vitro

The effect of mild hyperthermia on a cultured rat malignant fibrous histiocytoma (MFH) cell line, MFH-2NR, was investigated. MFH cells in log-phase (growing phase) were heated at 41 degrees-44 degrees C for 1 hr. Hyperthermic treatment at 41 degrees C did not substantially affect cell proliferation and treatment at 44 degrees C caused necrosis. After hypothermic treatment at 42 degrees or 43 degrees C, proliferation of MFH cells was arrested and morphological changes characteristic of apoptosis, cell shrinkage accompanying apoptotic bodies and chromatin condensation, became apparent. Hyperthermia-induced apoptosis was further confirmed by terminal deoxynucleotidyl transferase staining and a ladder pattern on agarose gel electrophoresis. Flow cytometric analysis indicated that the population in the G1 phase of the cell cycle significantly decreased with a concomitant increase in apoptotic cells, indicating that apoptosis might occur mainly in the G1 phase population.