[IMMEDIATE RADIOBIOLOGICAL EFFECTS IN MICE FOLLOWING γ-IRRADIATION BY LOW DOSES].

Outbred CD-1 mice females aged 4 to 4.5-months were investigated in 21-22 hours following total γ-irradiation at 10, 25, 50, 75, 100 and 200 mGy. Loss in bone marrow karyocytes, as well as spleen and thymus mass reductions were significant in the group of animals irradiated at 50 and 200 mGy and less dramatic in mice irradiated at 75 mGy. The orientative-trying behavior reaction (OTBR) in the open field tested in 19-20 hours after exposure to 10 and 25 mGy was reliably stronger than in the group of biological control; however, emotional status (ES) in the animals that received 10 mGy dropped significantly. Mice irradiated at 50 mGy were found to weaken the grip of their front limbs. Dose levels differing in opposite radiobiological effects on the parameters under study were established. Doses in the range from 10 to 25 mGy maximized OTBR and ES, while doses of 50, 100 and 200 mGy produced high reactions of the immune and hemopoietic organs.

[Modification of the cytogenetic effects of irradiation by water with the reduced content of deuterium and heavy isotopes of oxygen].

The influence of light water with the reduced content of heavy stable isotopes of oxygen and hydrogen (deuterium) on the cytogenetic status of irradiated animals was investigated. In mice, hybrids of the first generation (CBA x C57B1) F1, the increase in the output (two-fold at the dose of 2 Gy) of aberrant mitoses in the cells of bone marrow and the decrease in the duration of the mitotic index of the first cellular cycle occurred under the influence of the two week maintenance before the irradiation on light water with ppm 35 obtained by the method of rectification as compared with the irradiated animals that were kept on the distilled water. It has been discovered that 24 h after irradiation the number of leukocytes in the group which consumed light water is lower than that in the animals that were contained on the distilled water. Moreover, the cellularity of the bone marrow in the group which consumed light water was higher than that in the animals that were contained on distilled water. The prolonged application of light water before irradiation (for 14 days) led to an increase in the sensitivity of the chromosomal apparatus of mice to γ-irradiation against the background of an increase in the mitotic activity of cells.

[Proton three-demensional conformal radiosurgery of arteriovenous malformation of the brain].

The proton beam radiosurgery was performed to 65 patients with brain AVM since December, 2001 till February, 2012, in Joint Institute for Nuclear Research, Dubna, Russia. We have analyzed data for 56 patients. The follow up time varied from 24 to 109 months. The volumes of brain AVMs varied from 0.92 to 82 cc. The mean isocenter dose was 24.61 +/- 0.12 Gy E. The edge of the target was included in 70-90% isodose. The proton beam surgery was splitted in two similar doses and delivered in two consecutive days in vast majority of patients. Ten patients were missed for follow up due to some reasons. The radiosurgery was resulted in full obliteration of AVM in 23 from remaining 46 (50%) patients. There was full obliteration in 46.6% of patients with volume of AVM 10-24.9 cc; and this rate is significantly more than for photon radiosurgery of same size brain AVM. The partial obliteration was obtained in 21 patients. Only one patients suffered hemorrhage from partially obliterated AVM. We could not see any effect in 2 patients. There were delayed radiation toxicity in 5 patients in 12 months after treatment: in 4 patients, these reactions were assessed as 2 according to RTOG scale and were dissipated in 1 month after commencement of corticosteroid treatment. There was radiation necrosis in one patient, and it was relieved in 12 months after several courses of dehydration and corticosteroid therapy. So, proton beam therapy is effective and safe modality for treatment of inoperable brain AVM, especially of middle- and large size.

[Effect of a mineral organic complex on mice radioresistance].

Experiments showed that drinking water supplemented with a complex of 12 microelements and organic acids stimulates body mass gain and strengthening of radioresistance in mice. Obviously, availability of water with the mineral and organic complex before and after irradiation was the factor in survival of a part of mice exposed to the absolutely lethal dose (7.6 Gy from gamma-quanta 60Co) and reduction of chromosomal aberrations rate in bone marrow cells in consequence of nonlethal (1 Gy) irradiation.

[Radiomodifying properties of deuterium-depleted water with poor content of heavier isotopes of oxygen].

Experiments were performed with outbreed mice CD-I and hybrid mice (CBA' C57BI)F1. Seven to 21 days before irradiation, the mice had continuously consumed light-isotope water (35 ppm) produced by rectification w/o secondary treatment. Dose of single gamma-irradiation ranged from 4 to 8.5 Gy. The radiomodifying effects included statistically reliable reductions in survivability and life span, loss of body mass, and decreases in marrow myelokaryocytes and peripheral leukocytes. In 8-9 days after irradiation, spleen mass in the experimental mice was found enlarged as compared with the controls.

[Modification of radiation damage to biological objects by lasers].

A series of experiments had the purpose to study effects of gamma-rays 60Co (5 Gy) and the combined effects of laser 650 nm (1 mJ/cm2) and gamma-rays 60Co (5 Gy) on survivability, body mass, integument and mitotic index of marrow cells (MC) of young mice C57BL/6. Laser was applied to the mouse hairy back only. Ten months of gamma-irradiation brought death to 50% of mice; the combined irradiation killed only 30%. Starting on month six after gamma-irradiation, body mass was less in comparison with mice exposed to the combined irradiation. In addition, all mice lost body mass sharply before death. All gamma-irradiated mice were touched with grey over the period of 30 days; in 40 days, 10 of 20 mice had incipient local radiation alopecia on the back that passed fully within next month. However, all mice developed radiation ulcers on the fourth month since irradiation. Two mice formed also neck tumors. In 5 months tails fell off in 2 mice. Some grey streaks appeared on mice exposed to the combined irradiation 3 months later only; three mice remained black throughout the follow-up. Alopecia was found in three survivors in 5 months after irradiation. Mitotic activity of marrow cells obtained from mice on day 15 since exposure to lasing and combined irradiation was higher in comparison with cells from intact mice. In a year, the MC mitotic index was higher in mice exposed to the combined irradiation as compared with the gamma-irradiated mice.

[Some specific effects of the combined exposure to gamma and laser radiations on survivability of mouse fibroblasts in vitro].

Effects of the combined exposure to gamma-rays and laser radiation (633 nm) on survivability of fibroblast cells C3H/10T1/2, clone 8 were studied. First, a monolayer of fibroblast cells on a plastic vial wall was irradiated by gamma-rays and then the whole wall surface (25 cm2) or the central part of the vial (1 CM2) only was exposed to laser radiation. Forty minutes after exposure the cells were dispersed in 0.25% solution of tripsin and inoculated in vials for survivability determination. The experiments evidenced that the radioprotective effect of laser is essentially invariant no matter the size of a laser-irradiated monolayer. Adding the nutrient medium from the vials subjected to the combined irradiation to the gamma-irradiated vials also increased cell survivability. Cells from the cultivated blend of suspensions (exposed to ionizing and optic radiations and to ionizing radiation only) also exhibited a better survivability. A bystander radioprotective effect of laser can be assumed.

[Manifestation of the adaptive response and bystander-effect of C3H10T1/2 fibroblasts irradiated by protons and gamma-rays].

Adaptive response and bystander-effect were studied in mice fibroblasts irradiated by gamma-rays and protons with the energy of 150 MeV Monolayer of fibroblasts cultivated on the wall of a plastic vial first were exposed to 2 and 4 cGy of ionizing radiation (presumably adaptive doses) and later, after 40-min. or 16-hr. period at 37 degrees C, to damaging 4 Gy. To study the bystander-effect, either the whole vial surface (25 cm2) or central area (1 cm2) were irradiated by a beam of protons. The results showed that the preliminary gamma-irradiation 40-min. or 16-hr. before exposure to the damaging dose equally alleviates the harmful effect of protons on fibroblasts. The adaptive response was observed as in the cells subjected to the direct irradiation by protons at 4 Gy, so in bystander-cells. When protons were used for adaptive irradiation, the response was visible only to the dose of 4 cGy in fibroblasts exposed to gamma-radiation 16 hrs. later. In all the rest cases, proton- and gamma-induced damages added together. Besides, the experiments showed that the adaptive effect of protons is passed on to bystander-cells. Adaptive and damaging gamma-irradiation evoked the response invariably.

[Radioprotective effect of helium-neon laser radiation for fibroblast cells].

Effects of combined exposure to 633-nm laser waves and gamma-radiation, and laser waves and protons with the energy of 150 MeV on survivablilty of mice fibroblast cells C3H10T1/2 were compared. Cell suspension (1 - 5 x 10(5) cells/ml) was distributed in 2-ml plastic vials with 1 cm in diameter time interval between two exposures in a combination was no more than 60 s. immediately after exposure a required quantity of cells was inoculated in special vials for survivability assessment. Based on results of the experiment, preliminary and repeated laser treatment was favorable to survivability of fibroblast cells subjected to gamma- or proton irradiation (dose variation factor was within 1.3 to 2.2). Simultaneous exposure of C3H10T1/2 cells to the laser and proton beams also increased their survivability. The radioprotective effect of the helium-neon laser on fibroblasts earlier exposed to ionizing radiation is of chief interest, as most of the present-day radioprotectors are effective only if introduced into organism prior to exposure.

[Dependence of mice fibrobslasts radiosensitivity on the exposure conditions].

In the scientific literature there is lengthy discussion concerning utilization of low-dose hypersensitivity and bystander in radiation therapy which inspired us to investigate these effects using cells of mice fibroblasts C3H10T1/2. Irradiated were monolayers of fibroblasts cells cultivated on wall of plastic vials. To study the bystander effect, the therapeutic proton beam with the onset energy of 150 Me V was directed at the whole wall (25 cr2) or only the central area of 1 cv(2). In an hour after irradiation the cells were dispersed in 0.25 % tripsin solution and inoculated in vials for survivability analysis. In both cases survivability of the cells was essentially equal following irradiation by 0.5 Gy, 2 Gy and 5 Gy. The same observation was made also after fractionated irradiation by the total doses of 10 and 20 Gy (2 Gy per a day, 5 times a week). In these experiments, each time another area (1 cm(2)) of the vial wall was subjected to irradiation. Three 0.4 Gy fractionated irradiations of cells C3H10OT1/2 per a day (5 times a week) by gamma-source 60Co with an interval of 3 hours showed that the total dose of 6 Gy and 12 Gy gathered by this protocol had the strongest lethal effect on fibroblast cells as compared with the daily one-time irradiation by 1.2 Gy. According to these results, detail studies of the low-dose hypersensitivity and bystander effects may come up with their effective utilization in radiation therapy.

[Effectiveness of the biological action of protons and gamma-radiation on cells C3H10T1/2].

Relative biological effectiveness (RBE) of the therapeutic proton beam with an energy of 150 MeV was measured during fractional irradiation of mice fibroblasts C3H101 T1/2 by 4.0 Gy per day, 5 d/w with the total dose of 40 Gy. Lethal effectiveness of the beam at different points of modified Bragg's peak (width of the flat apex = 3.7 cm) was evaluated and effects of acute single gamma-radiation (6CO) of cells were investigated. Results were compared with the data of fractional irradiation to assess reparation processes. It was shown that survivability of the cells in three points of Bragg's peak was essentially the same but a bit higher at the point of entry. Proton RBE in the experiment was equal to zero relative to gamma-radiation. Difference between fractional and acute irradiation leveled off with rising doses; however, the reparative processes still had a place even at 20 Gy.