Behavioral performance and microglial status in mice after moderate dose of proton irradiation.

Cognitive impairment is a remote effect of gamma radiation treatment of malignancies. The major part of the studies on the effect of proton irradiation (a promising alternative in the treatment of radio-resistant tumors and tumors located close to critical organs) on the cognitive abilities of laboratory animals and their relation to morphological changes in the brain is rather contradictory. The aim of this study was to investigate cognitive functions and the dynamics of changes in morphological parameters of hippocampal microglial cells after 7.5 Gy of proton irradiation. Two months after the cranial irradiation, 8- to 9-week-old male SHK mice were tested for total activity, spatial learning, as well as long- and short-term hippocampus-dependent memory. To estimate the morphological parameters of microglia, brain slices of control and irradiated animals each with different time after proton irradiation (24 h, 7 days, 1 month) were stained for microglial marker Iba-1. No changes in behavior or deficits in short-term and long-term hippocampus-dependent memory were found, but an impairment of episodic memory was observed. A change in the morphology of hippocampal microglial cells, which is characteristic of the transition of cells to an activated state, was detected. One day after proton exposure in the brain tissue, a slight decrease in cell density was observed, which was restored to the control level by the 30th day after treatment. The results obtained may be promising with regard to the future use of using high doses of protons per fraction in the irradiation of tumors.

Growth Induction of Solid Ehrlich Ascitic Carcinoma in Mice after Proton Irradiation of Tumor Cells Ex Vivo.

This study presents data on the growth rate and frequency of induction of the solid form of Ehrlich's ascites carcinoma (EAC) in mice in the short and long term after inoculation of ascitic cells irradiated ex vivo with a proton beam in the dose range of 30-150 Gy. It was shown that the growth rate of solid tumors after inoculation of irradiated cells ex vivo coincided with the growth of tumors in the control group. The frequency of tumor induction in mice after inoculation of EAC cells irradiated at a dose of 30 Gy was 80%, 60 Gy-60%, 90 Gy-25%, and 120 Gy-10%; at irradiation at a dose of 150 Gy, no tumors appeared during the entire observation period. Thus, we determined the dose of proton radiation required to eliminate tumor cells and/or signaling factors that can lead to the induction of tumor growth of EAC in mice.

Assessment of the Relative Biological Efficiency of Pencil Beam Scanning of Protons in Mice in Vivo.

The effect of proton pencil beam scanning in the dose range of 4.5-15 Gy on the radiosensitivity of mice under irradiation in two regions of the Bragg curve was studied according to the criteria of 30-day survival, dynamics of death, and average lifespan of mice. The relative biological effectiveness (RBE) value of protons relative to X-ray radiation before and at the Bragg peak determined by the LD50/30 index was 0.86 and 0.94, respectively, and by the criterion of 30-day survival at a dose of 6.5 Gy it was 0.83 and 0.84, respectively. With similar RBE values for protons in different regions of the Bragg curve, significant differences in the dynamics of the course of radiation sickness were revealed, which indicates different damage to critical systems and organs of animals and the induction of compensatory mechanisms involved in the formation of stress responses at the organismal level.

Combined Effect of Neutron and Proton Radiations on the Growth of Solid Ehrlich Ascites Carcinoma and Remote Effects in Mice.

The combined effect of the irradiation with a proton pencil scanning beam (PBS) at a total dose of 80 Gy and neutron radiation at a dose of 5 Gy on the growth of solid Ehrlich ascites carcinoma (EAC) and the remote effects in tumor-bearing mice was studied. Combined irradiation of mice with neutrons before and after irradiation with PBS, as well as irradiation only with PBS, effectively suppressed the growth of solid EAC within 1 month. In terms of the frequency and severity of radiation-induced skin reactions of mice observed 15-40 days after therapy, neutron irradiation after the irradiation with PBS showed better values of these parameters as compared to only PBS; however, exposure to neutrons before PBS was more damaging as compared to the other two options. It was also shown that the tumor relapse rate in the groups of animals with combined irradiation was higher, and the total lifespan was lower than the group of mice irradiated with PBS alone.

The Effect of Low and Medium Doses of Proton Pencil Scanning Beam on the Blood-Forming Organs during Total Irradiation of Mice.

The aim of this work was to study the effect of proton pencil beam scanning in the Bragg peak in the dose range of 0.1-1.5 Gy on the induction of cytogenetic damage in the bone marrow, reactive oxygen species (ROS) production in whole blood, and the state of lymphoid organs after total body irradiation of mice. Irradiation was carried out in the Prometeus proton synchrotron (Protvino) in the Bragg peak with proton energy at the output of 90-116 MeV. It was found that, under irradiation of mice in the range of low and medium doses of proton pencil beam scanning in the Bragg peak, the relative biological effectiveness (RBE) according to the criterion of cytogenetic changes was 1.15. In addition, it was found that the pathophysiological effect on the lymphoid organs and the production of ROS by blood cells were different as compared with the effect of X-rays.