A. M. Babsky1,2, M. Yu. Klevets2, N. Bansal1
The direct measurement of temperature in subcutaneously (sc) implanted tumors shows that the actual tumor temperature is by 3–4 °C lower than the normal body temperature. Thus, the temperatures usually used for tumor hyperthermia are in fact heating the sc-tumors from 33 to 37 °C. The temperature increase during the perfusion of radiation-induced fibrosarcoma (RIF-1) cells from 33 to 37 °C caused a reversible increase in intracellular 23Na ([Na+]i) NMR signal intensity by 50–60%. This heating significantly decreased the intracellular pH (pHi) in 5 min, but it returned back to the baseline level during the heating period. The ?ATP/Pi remained generally unchanged throughout the experiment. Monensin, an antitumoral drug and Na+ ionophor, increased [Na+]i by 20% during cell superfusion without heating. When combined, monensin did not increase the heating effect on [Na+]i. However, when monensin was added to the superfusion media, the [Na+]i level did not return to baseline during post-heating recovery, but instead started to increase again. Monensin did not significantly change pHi and ?ATP/Pi. Our data and the literature show that monensin can accelerate the processes leading to the collapse of the transmembrane Na+ gradient and thus can increase the thermo-sensitivity of tumor cells.
Key words: RIF-1, temperature, sodium, monensin, pH, NMR.
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