Pylypchuk O. Peculiarities of co-mutagen effects on the radiosensitivity of human peripheral blood lymphocytes chromosomes

The thesis is devoted to the study of regularities of co-mutagens impact on human chromosomes radiosensitivity in peripheral blood lymphocytes of healthy individuals and cancer patients. Co-mutagenic impact of verapamil as a calcium channel blocker and ascorbic acid as an antioxidant have been studied using the test system of peripheral blood lymphocytes of healthy individuals. For the first time it was determined that co-mutagenic effects in exposed human cells depended on the ionizing radiation dose, cell radiosensitivity as well as drug concentrations and specificity of their action. It was shown that co-mutagens, verapamil and ascorbic acid, at various concentrations induced effects of low dose radiation, it increasing total frequency of chromosomal aberrations in lymphocytes healthy individuals. It was revealed co-mutagenic effects of ascorbic acid in therapeutic concentration (20,0 mg/ml of blood) and verapamil in high concentration (4,0 mg/ml of blood) in in vitro low-level exposed lymphocytes of the primary cancer patients. The ability of ascorbic acid to change DNA structural organization of the irradiated lymphocytes of cancer patients promoting microsatellite instability of the genome has been detected. It was shown that analyzed co-mutagens stimulated mitotic index of irradiation lymphocytes of healthy individuals depending on concentration and dose. Thus, co-mutagenesis developing in exposed human cells is based on the processes of chromosomal and microsatellite instability, apoptosis and stimulation of cell proliferation.