Enhanced Radiosensitivity of Tumor Cells Treated with Vanadate in Vitro

Vanadate 처리가 종양세포의 방사선 감수성에 미치는 영향

Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cellls but not CCL-120 normal cells to radiation. Ouabain inhibits the $Na^+-K^+$-pump rapidly thus it increases intracellular Na concentration, Vanadate which is distributed extensively in almost all living organisms is known to be a $Na^+-K^+$-ATPase inhibitors, This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of $Na^+-K^+$ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMC cells and frypan blue dye exclusion test for L120, and spleen cells. Measurements of $Na^+-K^+$-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined $10^{-6}M$ vanadate and radiation treated cells were done. The results were summerized as fellows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Mininum or no cytotoxicity was seen with vanadate below concentration of $10^{-6}M$. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. e. 2- Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. $Na^+-K^+$-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiaiton itself inhibited $Na^+-K^+$-ATPase activity of tumor cell with high $Na^+-K^+$-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with orginal $Na^+-K^+$-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized tumor cells to radiation. Inhibitory effect of vanadate on $Na^+-K^+$-ATPase activity might be one of the contributing factors for radiosensitization to tumor cells which has greater enzyme activity than that of normal cell. It was suggested vanadate could be used as a potential radiosensitizer for tumor cells.