ENHANCEMENT OF OXIDATIVE CELL INJURY AND ANTITUMOR EFFECTS OF LOCALIZED 44-DEGREES-C HYPERTHERMIA UPON COMBINATION WITH RESPIRATORY HYPEROXIA AND XANTHINE-OXIDASE

The effects of respiratory hyperoxia (RH) and xanthine oxidase (XO) du ring localized hyperthermia (HT) were investigated by determining mark ers of oxidative damage to lipids and proteins and tumor growth. Anest hetized rats with s.c. DS-sarcomas underwent one of the following trea tments: (a) localized saline-bath HT (60 min, 44 degrees C); (b) HT RH (100% O-2); and (c) HT + RE + XO (15 units/kg i.v.). Sham-treated a nimals served as controls. Tumors were investigated for: (a) thiobarbi turic acid-reactive substance formation and protein-bound 4-hydroxynon enal, as indicators of lipid peroxidation; (b) reactive oxygen-mediate d protein modifications; (c) apoptosis; and (d) tumor volume growth. U pon treatment, increases in thiobarbituric acid-reactive substances, p rotein-bound 4-hydroxynonenal, protein-associated carbonyl functions, and number of cells undergoing apoptosis were found in tumor tissue, t ogether with an inhibition of tumor growth. When treatment groups were compared, effects in the group HT + RH + XO were generally most prono unced. These findings indicate that the antitumor effect of HT is at l east partially mediated through the selective induction of lipid perox idation and oxidative injury in tumor cells, leading to apoptosis. Thi s effect was enhanced by adding RH or RH + XO, presumably due to enhan ced tissue damage following an increased formation of reactive oxygen species, with higher levels of lipid peroxidation and protein oxidatio n.