Nitric Oxide Radical-induced Radioadaptation and Radiosensitization Are G2/M Phase-dependent

The aim of this study was to examine biological effects of nitric oxide (NO) on radiosensitivity and chromosome aberrations in different phases of the cell cycle in human cancer cells with a wild-type p53 (wtp53) genotype. H1299/wtp53 cells were pre-treated with isosorbide dinitrate (ISDN) at different concentrations or pre-irradiated with a low dose of X-rays, and then exposed to a high dose of X-rays. Cell synchronization was achieved with serum starvation. Cellular radiosensitivity, cell cycle distributions, and chromosome aberrations were assayed with colony-forming assays, flow cytometry and chromosome banding techniques, respectively. After treatment with ISDN at a low concentration or after an exposure to 0.02 Gy of X-rays, radioresistance and a reduction in the number of chromosome aberrations were observed mainly 17.5 h after plating mitotic cells. This radioadaptation effect was observed during a clearly shortened G(2)/M phase and a slightly prolonged S phase. In contrast, in the presence of a high concentration of ISDN, radiosensitization and the enhancement of chromosome aberrations were detected principally 17.5 h after plating mitotic cells, and this radiosensitization was observed during a significantly prolonged G(2)/M phase and a slightly shortened S phase. A range of concentrations of NO induced opposing effects on radiosensitivity and chromosome aberrations in human non-small cell lung cancer cells bearing wtp53 gene status, and these different effects produced by NO depended on the cell cycle phase.