Peculiarities of DNA damage caused by exogenous nitric oxide combined with fractionated low dose ionizing radiation in normal and tumor cells

Abstract

The aim of this study was to investigate the reaction of normal and tumor cells to genotoxic effect of widespread environmental factors — exogenous nitric oxides and ionizing radiation. Methods: The animals were treated with NO (125 mg/m3) and low dose ioni­zing radiation (10 acute exposures with 0.1 Gy each). Genotoxicity was estimated in vivo in rats peripheral blood lymphocytes, bone marrow cells and tumor cells of Guerin carcinoma. DNA damages were assessed by alkaline single-cell gel electrophoresis. Results: Exogenous nitric oxides as well as irradiation caused significant increase of DNA damage in all types of investigated cells. The genotoxic effect increased in the order: peripheral blood lymphocytes < bone marrow cells < Guerin carcinoma cells. The greatest genotoxic effect was registered in Guerin carcinoma cells on terminal phase of tumor growth in rats exposed to NO and low dose ionizing radiation. Conclusions: Long-term exposure to common environmental factors (exogenous nitric oxides and ionizing radiation) capable to induce DNA damage in diffe­rent cells. Severity of the genotoxic effect depends on cell type and nature of impacting factors. NO caused more significant DNA damage than low dose ionizing radiation but the highest level of DNA damage was observed after their joint action. Obtained results confirm the real threat of cancer risk increase under combined action of common environmental factors of different nature. Key Words: nitric oxide, nitrosative stress, ionizing radiation, tumor cells, DNA damage.