エールリッヒ腹水癌の温熱感受性に対するアミロライド誘導体 : MH-12-43の増強効果

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  • Enhancement Effect of Amiloride Derivative MH-12-43 on Thermosensitivity of Ehrlich Ascites Tumor Cells.

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Amilorid, 3, 5-diamino-6-chloro-N- (diaminomethylene) pyrazinecarboxamide, and its derivative MH-12-43, N-amidino-3-amino-6-chloro-5- (N-ethylisopropylamino) pyrazinecarboxamide, were studied for cytotoxicity, thermosensitivity and changes of intracellular pH (pHi) in Ehrlich ascites tumor cells (EAT cells). Similar cytotoxicities were observed in MH-12-43 at lower concentrations than amiloride. After treatment with 0.5 mM amiloride or 0.05 mM MH-12-43 at 37°C for 120 min, no decrease in survival rate were shown. The effects of hyperthermia at 42°C were enhanced by amiloride and MH-12-43, and the more decrease in suvival rate with 0.05 mM MH-12-43 was observed rather than that with 0.5 mM amiloride from hyperthermia at 42°C. The treatment of 0.5 mM amiloride or 0.05 mM MH-12-43 reduced pHi at 37°C, while the more reduction was observed by the treatment at 42°C. The reduction of pHi by 0.05 mM MH-12-43 was more substantial than that of 0.5 mM amiloride at 42°C. These suggest that the enhancement in the hyperthermic effects by amiloride or MH-12-43 may be due in part to a decrease in pHi.

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