Vovk A. Superoxide- and NO-dependent processes in the tumor growth

The dissertation is devoted to the role of nitric oxide (NO) and superoxide radicals in dysfunction of the electron transport chain (ETC) of mitochondria and the metabolism of iron under conditions of tumor process in vivo and in patients with rectal cancer (RC). In the experiment on a model of Lewis lung carcinoma (LLC) we have revealed that formation of NO-сeruloplasmin complexes in the blood of animals causes changes in the metabolism of iron. The data has been obtained on mechanisms of implementation of NO of tumor and antitumor effects depending on the dose of L-arginine: injection of L-arginine at a dose of 360 mg/kg body mass caused inhibition of tumor growth and reduction of metastasis; injection of L-arginine at a dose of 60 mg/kg body mass - stimulation of tumor growth. The NO-dependent mechanism of the change in oxygen metabolism in mitochondria of RC cells in patients with stage II-III has been found, and a correlation between the level of NO and stage of disease (r=0,49; р<0,05) has been revealed. The scientific data on the presence of significant correlation between the level of LF and "free" iron in RC tissue (r=0,51) and the degree of tumor differentiation (r=-0,61) have been supplemented. A decrease in сeruloplasmin level in the blood of patients with RC, formation of NO-сeruloplasmin complexes have been revealed, and an inverse correlation between the content of сeruloplasmin and "free" iron has been found (r=-0,58; p<0,05). It has been revealed that the level of superoxide- and NO-generating activity of blood neutrophils was significantly correlated with stage of tumor process and tumor size. The data on relationship between the rate of generation of superoxide radicals by platelets with the stage of tumor process (r=0,74), the size of tumor (r=0,65) and the level of fibrinogen (r=0,59) in the blood serum have been supplemented.