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Stereotactic radiosurgery with the usage of different kinds of radiation has been of great importance in the treatment of non-operating arteriovenous malformation (AVM) of the brain for the last three decades. Proton beams have unique physical properties that are favorable for stereotactic radiosurgery or conformal radiation therapy: small lateral divergence, sharp lateral penumbra, final and easy controlled range in tissue, depending of beam energy and tissue density, increasing of dose deposition at the end of range, so called Bragg peak. Modern and up-todate technology of three-dimensional proton radiosurgery AVM of the brain which allows irradiating accurately AVM of the brain of any size, shape and location, was worked out and clinically approved in Medical Technical Complex after 2001 year. International report was used for the treatment of patients, according to it the target of irradiation was included into 70-80% isodose. The absorbed doses made 25 Gy-equivalent in the isocenter point (1 Grey-equivalent equals 1 Gy physical, multiplied by the relative biological effectiveness of the proton, which is 1.1). Irradiation treatment was conducted within 2 session for the two successive days. Proton radiosurgery based on this new technology was conducted on 39 patients suffering from AVM of the brain. The volume of the targets of irradiation was from 1.5 to 82.1 cm3 . Early result demonstrated that developed technique of proton irradiation allows to deliver proton dose to the target volume precisely. 272

Purpose: To study was to study the effect of GNP nanoparticles on tumor cells of human lung carcinoma A 549 when irradiated with protons. Materials and methods: Cell culture: Human lung carcinoma cells A 549. Gold nanoparticles Au/PEG 6000/W 200/30 nm: A colloidal solution of gold nanoparticles purchased from the firm M 9 Nanomaterials & Technologies was used in the work. Proton irradiation: The irradiation of cells was carried out on a therapeutic proton beam in the Medical and Technical Complex of the Laboratory of Nuclear Problems Joint Institute for Nuclear Research. Determination of radiosensitivity of cells: By determining the clonogenic survival of cells. Determination of the genotoxic activity of nanoparticles under the action of proton irradiation: investigated using a micronucleus test with blocking cytokinesis. The genotoxicity of gold nanoparticles was estimated by the number of micronuclei per 1000 binuclear cells. Micronucleus were counted only in binuclear cells. At least 1000 binuclear cells were calculated for each dose, experiments were carried out in three repeats. Results: The frequency of micronucleus formation indicates an increase in the genotoxic effect of nanoparticles when irradiated with protons at a dose of 2 Gy. Proton irradiation caused an increase in the frequency of micronucleus formation depending on the concentration of nanoparticles. When irradiated with protons at a dose of 2 Gy in the presence and absence of nanoparticles, the difference in the frequency of micronucleus formation for the concentration of nanoparticles was 2.5 mg/ml – 1.1; for 5 mg/ml and 10 mg/ml – 1.2; for 15 mg/ml – 1.3 and for 30 mg/ml –1.5. Cell survival curves reflect a decrease in their survival rate when metal nanoparticles with high Z are added, which reflects the occurrence of radiosensitization effects. The gain for 10 % and 50 % survival rates is 1.4 and 2.5, respectively. Conclusions: Under the influence of proton irradiation, the genotoxic activity of gold nanoparticles in human lung carcinoma cells A 549 increases, depending on their concentration. The survival rate of human lung carcinoma A 549 cells irradiated with protons in the presence of gold nanoparticles decreases.

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