Enhancement of γ-irradiation genotoxicity in human lung carcinoma A 549 cells in the presence of gold nanoparticles

Introduction. One of the main problems of radiotherapy is the lack of selectivity in the absorption of radiation energy by tumor cells due to the similar energy-absorbing properties of tumor and healthy tissues. An increase in the absorbed dose can be achieved by administering or delivering substances to tumor cells with a significantly larger radiation absorption cross-section than in normal cells. These are chemical elements with a high atomic number Z, more than 52 (I, Gd, Au, Pt, etc.). Due to the greater probability of interaction of such elements with radiation, it is possible to achieve a local increase in the absorbed dose in the area of accumulation of a substance with a high atomic number. The resulting secondary short-range radiation localizes the energy release near these elements and affects only nearby biological structures. The aim of the research is to study the genotoxic effect of γ-irradiation on tumor cells of human lung carcinoma A 549 in the presence of gold nanoparticles. Materials and methods. Human lung carcinoma cells A549 were cultured under standard conditions. Gold nanoparticles (Au/PEG6000/W 200/20 nm) were added to the culture medium 24 hours before irradiation at a concentration of 0.1; 2.5; 5; 10; 15; 30 μg/ml. Before irradiation, the medium with nanoparticles was removed, the cells were washed twice of PBS and a fresh medium was added. The cells were exposed to 60Co γ-radiation at a dose of 2 Gy. The genotoxic effect of gold nanoparticles (GNP) was studied by a cytokinesis-blocking micronucleus test (CBMN). Results. The number of micronucleus in A549 cells cultured in the presence of GNP in the concentration of 0.1-30 μg/ml is at the control level. There is an increase in the number of micronucleus under γ-irradiation of cells treated with GNP at a dose of 2 Gy compared to untreated cells. The GNP concentration of 15 μg/ml is optimal for increasing the efficiency of γ-irradiation at a dose of 2 Gy for cells A549. The proliferation index (CBPI) was calculated for cells exposed to γ-radiation at a dose of 2 Gy for two groups of cells, untreated and treated with GNP. The proliferation index within each group is approximately the same. However, in cells irradiated in the presence of GNP, the proliferation index is lower than in untreated cells. At a concentration of 0.1, 2.5, 5, 10 μg/ml, the cytostatic effect of GNP does not significantly differ from the control samples (irradiation of 2 Gy without GNP). The tendency to increase cytostatic activity is observed at concentrations of 15 and 30 μg/ml in combination with γ irradiation. Conclusions. GNP in combination with γ-irradiation enhances the genotoxic effect on the tumor cells A549. The frequency of micronucleus increases and the proliferative index decreases in cells irradiated together with GNP. (author)