부산대학교 도서관

The acute effects of hyperthermia on intracellular Na+ (Nai+), bioenergetic status and intracellular pH (pHi) were investigated in superfused Radiation Induced Fibrosarcoma-1 (RIF-1) tumour cells using shift-reagent-aided 23Na and 31P nuclear magnetic resonance (NMR) spectroscopy. Hyperthermia at 45°C for 30 mm produced a 50% increase in Nat, a 0.42 unit decrease in pHi and a 40-45% decrease in NTP/Pi. During post-hyperthermia superfusion at 37° C, pH, and NTP/Pi recovered to the baseline value, but Nat initially decreased and then increased to the hyperthermic level 60 mm after heating. Hyperthermia at 42°C caused only a 15-20% increase in Nat. In the presence of 3 µM 5-(N-ethyl-N-isopropyl)amiloride (EIPA), an inhibitor of the Na+/H+ exchanger, the increase in Nai+ during 45°C hyperthermia was attenuated, suggesting that the heat-induced increase in Nat was mainly due to an increase in Na+/H+ anti-porter activity. EIPA did not prevent hyperthermia-induced acidification. This suggests that pHi is controlled by other ion exchange mechanisms in addition to the Nai+/H+ exchanger. EIPA increased the thermo-sensitivity of the RIF-1 tumour cells only slightly as measured by cell viability and clonogenic assays. The hyperthermia-induced irreversible increase in Nat suggests that changes in transmembrane ion gradients play an important role in cell damage induced by hyperthermia. [ABSTRACT FROM AUTHOR]