Role of nitric oxide radicals in cancer therapy with heavy ion-beams

The Purpose of this study was to investigate whether radiation adaptive responses were induced after irradiation with accelerated carbon ion beams. Human non-small cell lung carcinoma (H1299) cells transfected with wild-type p53 (H1299/wtp53 cells) and normal fibroblast (AG1522) cells were used in the present study. The cells were irradiated with accelerated carbon ion beams (0.02 Gy, 290 MeV/u, 70 keV/μm) or X-rays (0.02 Gy, 1 mA, 130 kVp) as priming irradiations. After priming irradiation, the cells were irradiated with carbon ion beams (0-3 Gy, 290 MeV/u, 70 keV/μm) or X-rays (0-6 Gy, 5 mA, 130 kVp) as challenging irradiations. Then, the cells were allowed forming colonies. A significant radioresistance of H1299/wtp53 cells was observed when the cells were irradiated 6-12 h after the priming irradiation with X-rays at 0.02 Gy. Also, a significant radioresistance of H1299/wtp53 cells was observed when the cells were irradiated 6-24 h after the priming irradiation with accelerated carbon ion beams at 0.02 Gy. These responses were partially suppressed by the addition of NO radical scavenger, carboxy-PTIO at 10 μM to medium. Our findings suggest that high LET radiation (carbon beams) can induce radiation adaptive responses as well as low LET radiation and that NO radicals considerably contribute to the induction of radiation adaptive responses. (author)