Muzalov I. Peculiarities of formation and implementation of genotoxic effects under combined exposure to exogenous nitric oxides and ionizing radiation in health and tumor development

The thesis is devoted to defining the role of environmental factors of different nature - exogenous nitric oxide (NO) and ionizing radiation (IR) - in the formation of genotoxic damage, malfunction of repair and change of pro/antioxidant processes balance in normal and malignant cells in tumor bearing animals. The effect of NO and IR in vivo and in vitro is proved to cause genetic instability forming prompt (single-strand (SSBs) and double-strand breaks (DSBs)) and delayed DNA damage in the form of thermally labile sites (TLS) in peripheral blood lymphocytes (PBL), bone marrow cells (BMC) and Guerin carcinoma cells (GC). Maximal genotoxic effect was observed under combined exposure to both factors during the growth of GC. It was established that the combined effect of NO and IR in vitro reduces the intensity of PBL SSBs, DSBs and TLS repair in 1.2 - 2.2 times. SSBs and DSBs repair activity inversely depended on IR dose. In all cases, the impact of NO on inhibition of repair processes was prevalent. Primary DNA damage, caused be the joint effect of NO and IR, are implemented as chromosome aberrations. Prevalence of chromatide-type aberrations (in 3.8 times) indicates the dominant role of NO in observed genotoxic effects. It was proved that genotoxic effects of NO and IR correlates with the imbalance of pro- and antioxidant processes with accumulation of lipid peroxidation products, free radicals and antioxidant enzyme dysfunction. Investigated the biological characteristics of GC growth under joint action of exogenous NO and IR. Previous NO inhalation and irradiation of animals led to a significant intensification of tumor growth, especially IR treated.