Significance of free radicals in the cytotoxic process of hyperthermia
Gi, H.
Nihon Geka Hokan. Archiv für Japanische Chirurgie 53(6): 742-755
1984
ISSN/ISBN: 0003-9152 PMID: 6100039 Document Number: 224926
The effects of hyperthermia on the generation of free radicals and their cytotoxicity were investigated by using a rat neurogenic tumor (T1) cells and hot water bath hyperthermia. Hydroxyl radicals were measured by bleaching of p-nitrodimethylaniline, and superoxide radicals were measured by reduction of nitroblue tetrazolium. The production of radicals were increased on hyperthermia. Hydroxyl radicals produced by hyperthermia at 42.degree. C for 30 min were equivalent to those produced by Linac irradiation of 1200-1400 rad. The combined use of 120 .mu.g/ml of superoxide dismutase (SOD) and 100 .mu.g/ml of catalase significantly inhibited the decrease of colony formation after hyperthermia at 42.degree. C for 30 min, while either enzyme alone showed no effects. Hydroxyl radicals evidently play a role in the mechanism of cytotoxicity of hyperthermia. The influence of several kinds of radical scavengers in relation to hyperthermia was studied. Dimethylsulfoxide (DMSO) significantly decreased the cytotoxicity due to hyperthermia at the same concentration that protected the cytotoxicity due to irradiation. Mannitol tended to inhibit the cytotoxicity of hyperthermia at 10 mM concentration. Misonidazole, which is an electron affinic radiosensitizer, showed no synergism with hyperthermia in this system where the cells were aerobic. Vitamin E did not affect the toxicity of hyperthermia. On the other hand, vitamin C, which is known to produce a large amount of various radicals during self-oxidation, markedly enhanced the cytotoxicity of hyperthermia at 45.degree. C depending on concentrations. Free radicals apparently take important part in the cytotoxic process of hyperthermia. Free radicals may depress or inhibit the repair of sublethal damage of DNA which had been brought about by hyperthermia, or enhance the lethal damage. In order to further establish the significance of free radicals in the cell killing process in hyperthermia, it is more important to investigate the fundamental mechanism at the electron and molecular levels.