Elevation of extracellular adenosine induces radioprotective effects in mice.

The radioprotective effectiveness of the elevation of extracellular adenosine induced in mice by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate, a soluble adenosine pro-drug, was evaluated. Based on survival studies, endogenous hemopoietic spleen colony formation, and the postirradiation behavior of bone marrow granulocyte-macrophage colony-forming cells (GM-CFC), it was demonstrated that the combined administration of dipyridamole and AMP protects mice when given either 15 or 60 min before irradiation. It could be deduced that the radioprotective action is induced by at least two independent mechanisms: (1) protection by hypoxia as a result of the effect of the treatment on the cardiovascular system, and (2) and enhanced regeneration of the hemopoietic stem cells due to either enhanced postirradiation repair or an increased proliferation of the hemopoietic stem cells. Both of these protective mechanisms, which are able to increase the regeneration of hemopoiesis, seemed to be effective in enhancing the survival of mice given single radiation exposures, with a dose reduction factor for the LD50/30 of 1.11. The protective efficiency of the mechanisms enhancing the postirradiation recovery of hemopoiesis was also evident in experiments evaluating the survival of mice subjected to fractionated irradiation and a repeated administration of the protective agents.

Evaluation of the biological effects of police radar RAMER 7F.

This paper presents results of experiments on the effects of electromagnetic radiation in the millimeter range (frequency 34.0 +/- 0.1 GHz, power density 20 muW/cm2) emitted by a police radar device. Considering the physical properties of the radiation in millimeter range (skin effects), the experiments were carried out on hairless mice. The main physiological parameters tested were body mass, body temperature, peripheral blood, and mass and cellularity of several important organs. Critical organs, the skin, and cornea were examined by electron microscopy. Differentiation ability of hematopoietic cells, progenitors of granulocytes and macrophages, and DNA synthesis in the cornea were compared in irradiated and nonirradiated animals. None of the parameters tested was affected to an extent that would indicate the start of a pathological process or the risk of damage to genetic material.

Hematopoietic recovery in repeatedly irradiated mice can be enhanced by a repeatedly administered combination of diclofenac and glucan.

A combination of diclofenac and glucan administered repeatedly in a protective regimen in the course of repeated gamma irradiation of mice (6 x 2 Gy during 3 weeks) enhanced granulopoiesis and other indices of hematopoietic recovery investigated from 3 to 7 days after the last radiation exposure. Repeated administration of diclofenac or glucan alone or treatment of the mice with the diclofenac-glucan combination given once before the first or the last radiation exposure did not induce such effects. The protective effect of the repeatedly administered combination of the drugs was realized despite the fact that the response of the serum colony-stimulating activity to the repeated combined drug administration was decreased at the end of the treatment regimen compared to that of mice given this drug combination only once. The combined treatment is supposed to act via increased proliferation of the hematopoietic stem or progenitor cells. Additivity or even synergism of the hematostimulatory action of glucan and of the strengthening of positive control of cell proliferation achieved by removing negatively acting prostaglandins (diclofenac action) may account for the radioprotective effects observed.

Effects of microwaves on membranes of hematopoietic cells in their structural and functional organization.

The role of cell membranes in stimulating and inhibiting the effects of microwaves was investigated in experiments carried out with a suspension of murine bone marrow cells irradiated with microwaves in vitro [f = 2.45 GHz, CW, specific absorption rate (SAR) = 12 W/kg]. Results obtained by means of a structural probe, 2.4-TNS, indicate that no structural changes occur in the region of the protein-lipid interphase under conditions of short-term irradiation with microwaves that induced temperatures in the range 36-45 degrees C (exposure time 315 and 525 s, respectively). Investigation of one functional parameter--the ability to produce hematopoietic colonies in the spleen after transplantation of the bone marrow irradiated in vitro by microwaves--indicated the possibility of affecting stimulatory and inhibitory effects of microwaves by using a blocker of cell receptors, Trimepranol. The role of microwaves as a physical factor interfering in the process of cell proliferation at the level of receptor regulation is discussed.

[The effect of gas hypoxia (10% O2) and dextran sulfate on the radiosensitivity of the stem cells of the intestinal epithelium in mice]. / Vliianie gazovoi gipoksii (10% O2) i dekstran-sul'fata na radiochuvstvitel'nost' stvolovykh kletok kishechnogo épiteliia myshei.

Injection of dextran sulphate before irradiation was shown to protect jejunal epithelium stem cells (D0 increased from 1.13 to 1.82 Gy). The protective effect of a combination of dextran sulphate and gas hypoxic mixture (10% O2) did not exceed that of the administration of the gas hypoxic mixture (10% O2) alone.

CFU-S and haematopoietic microenvironment in mice after fractionated irradiation. A study on spleen colonies.

The paper is aimed at evaluating the quantity and quality of the haematopoietic stem cells, CFU-S, in the bone marrow and the functional effectiveness of the haematopoietic microenvironment of the spleen in two time intervals after repeated exposure of mice to doses of 0.5 Gy gamma-rays once a week (total doses of 12 and 24 Gy). After irradiation, bone marrow was cross-transplanted between fractionatedly irradiated and control mice. The parameter evaluated were numbers of spleen colonies classified into size categories. The data obtained provide evidence for a significant damage to the CFU-S, concerning both their number and proliferation ability, after both total doses used. The functional effectiveness of the haematopoietic microenvironment of the spleen was impaired only in bone marrow recipients receiving a transplant after having been exposed to a total dose of 24 Gy; this dose combined with subsequent pre-transplantation irradiation resulted in a marked suppression of cell production within the spleen colonies formed from a normal bone marrow on the spleens of fractionatedly irradiated mice.

Effect of dipyridamole and adenosine monophosphate on cell proliferation in the hemopoietic tissue of normal and gamma-irradiated mice.

Combined treatment with dipyridamole and adenosine monophosphate enhances cell proliferation in the hemopoietic tissue of normal and gamma-irradiated mice. This effect can be explained by the elevation of extracellular adenosine, and the receptor-mediated activation of the cell adenylate cyclase system.

Amelioration of radiation damage to haemopoiesis by Ivastimul, given after irradiation to mice protected by peroral cystamine.

The combined radioprotection by preirradiation peroral cystamine and postirradiation Ivastimul treatment was examined in sublethally and lethally whole-body gamma-irradiated mice. The enhancement of haemopoietic recovery and increased survival of irradiated mice was demonstrated when a single dose of Ivastimul was administered after irradiation. Ameliorative influence of combined radioprotection may be explained by the haemopoietic stem cell protection by cystamine and haemopoietic stimulation mediated by Ivastimul.

Radioprotective effect of dextran sulphate and aerogenic hypoxia on intestinal crypt stem cells in mice.

A single intraperitoneal injection of dextran sulphate given 6 h before irradiation produced higher numbers of microcolonies of intestinal crypt stem cells in whole-body irradiated mice than injection of saline in control mice. If dextran sulphate and hypoxia are combined, the radioprotective effect of hypoxia on intestinal crypt stem cells depends on the time interval between irradiation and administration of dextran sulphate.

Decrease in the number of progenitors of erythrocytes (BFUe, CFUe), granulocytes and macrophages (GM-CFC) in bone marrow of rats after a 14-day flight onboard the Cosmos-2044 Biosatellite.

A decrease in the number of progenitors of erythrocytes (BFUe, CFUe) and of granulocytes and macrophages (GM-CFC) in bone marrow was found in rats exposed to microgravitation during a 14-day flight onboard the Cosmos-2044 biosatellite when compared to control rats maintained under conditions of gravitation on the ground. The number of progenitors of both lineages of haemopoiesis was also decreased in synchronous control rats, thus suggesting that the pool of progenitors is influenced also by the action of the nonspecific space flight factors.

Radioprotection of hemopoiesis conferred by aqueous extract from chlorococcal algae (Ivastimul) administered to mice before irradiation.

In experiments on mice, single i.p. injections of aqueous extract from chlorococcal freshwater algae (Ivastimul) were found to increase their radioresistance. During the same period the number of spleen colony-forming units (CFUs) in the bone marrow and spleen and their proliferation activity increased. The amount of granulocyte-macrophage colony-forming cells (GM-CFC) in the bone marrow grows and the colony-stimulating activity (CSA) of the blood serum of mice is elevated at an early period after injection of the substance. The recovery of the CFUs and GM-CFC pools in femoral bone marrow after irradiation proceeds at a faster rate in Ivastimul-treated animals than in control groups. The activation of the pool of hemopoietic stem cells and stimulatory effects of Ivastimul on granulocytopoiesis act favorably on the repair of radiation damage and on increased percentage of animals surviving lethal doses of gamma radiation.

Hydroxyurea as a suppressor of the radioprotective effect of dextran sulfate on bone marrow hemopoietic stem cells in mice.

The changes in hemopoiesis of mice following intraperitoneal administration of dextran sulfate (DS) 24 h before irradiation, as well as the effect of injecting them with hydroxyurea (HU), were analyzed. DS increased the proliferation activity and number of hemopoietic stem cells (CFUs) in the bone marrow. The content of CFUs in the bone marrow and the number of endogenous spleen colonies (ESC) of hemopoietic tissue were higher after irradiation in mice treated with DS than in control groups. The survival rate following a lethal radiation dose was also higher. Injection with HU decreased the number of CFUs in animals injected with DS to the level of controls and suppressed its radioprotective effect.

Increase in the capacity of bone marrow exposed to He-Ne laser radiation for growth of GM-CFC colonies in vitro.

Single exposure of murine bone marrow cell suspension to He-Ne laser radiation elevates the potential of haemopoietic stem cells for growth of GM-CFC colonies in vitro. The stimulatory action of He-Ne laser persists for 60 min after short-term irradiation.

Decrease in the number of progenitors of fibroblasts (CFUf) in bone marrow of rats after a 14-day flight onboard the Cosmos-2044 biosatellite.

A decrease in the number of progenitors of fibroblasts (CFUf) was found in bone marrow of rats that underwent a 14-day flight in the state of weightlessness onboard the Cosmos-2044 biosatellite, immediately after flight, when compared with rats maintained in control conditions of terrestrial gravitation. These changes may be explained by the action of specific factors of microgravitation.

The radioprotective effects of aqueous extract from chlorococcal freshwater algae (Chlorella kessleri) in mice and rats.

In experiments on mice and rats the effect was studied of a single administration of aqueous extract from chlorococcal freshwater algae - Ivastimul - on their radiosensitivity. After injection of this substance the number of haemopoietic stem cells in the bone marrow and spleen of mice (CFUs) increased, as did their survival after irradiation. Irradiation with a lethal dose of gamma rays 24 hours after the injection of Ivastimul is survived by a larger number of treated mice and rats than untreated ones. On the first day after the administration Ivastimul protects mice against brief and prolonged action of irradiation. The protective effect of Ivastimul was observed after intraperitoneal, intramuscular and subcutaneous administration.

Injection of dextran sulphate enhances in mice the stimulatory influence of serum on growth of haemopoietic tissue colonies (GM-CFC) in vitro.

A single i.p. injection of dextran sulphate elevates in mice the activity of blood serum for the stimulation of haemopoietic stem cell (GM-CFC) growth in vitro. Elevation of the stimulatory activity of serum persists up to 24 h after injection of dextran sulphate.

[Enhancement of the radioprotective action of gas-induced hypoxia by using dextran sulfate]. / Usilenie radiozashchitnogo deistviia gazovoi gipoksii dekstransul'fatom.

Mice of the strain (CBA X C57Bl) F1 injected with a single dose (40 mg.kg-1) of dextran sulphate (m.w. 5 X 10(5] were used to determine the survival rate after a lethal dose (13.0 Gy) of gamma irradiation, the number of haemopoietic stem cells in bone marrow (CFUs) and that of spleen endogenous colonies. Irradiation was performed in a hypobaric chamber at levels of 20%, 15%, 12% and 10% of the oxygen content. While in the control groups the levels of hypoxia showed a weak radioprotective effect in animals treated with DS, radioprotection was observed both in 10% O2 and in 15% O2. The animals treated exhibited a higher survival rate up to day 30 after irradiation, an elevated number of survived haemopoietic stem cells (CFUs) in the bone marrow, and increased number of endogenous spleen colonies, as compared with the control group. The potentiation of the radioprotective effect of hypoxia (10% O2) was observed till the end of observation (6th day after DS injection). The results obtained support an earlier observation that increased activity of haemopoiesis forms a convenient pool for the potentiation of the radioprotective efficiency of hypoxic hypoxia.

Effects of microwaves on the colony-forming capacity of haemopoietic stem cells in mice.

A suspension of bone marrow cells from femurs of female (CBA X C57Bl)F1 mice was exposed to 2450 MHz CW microwaves in a specially designed waveguide exposure system. The temperature of the suspension rose, during exposure to microwaves, from 20 degrees C to 45 degrees C, and at an interval within 20 degrees C to 45 degrees C the number of haemopoietic stem cells (CFUs) was determined by the spleen exocolony method. The time of exposure of bone marrow cells to each temperature studied was 20 s. Control suspensions of bone marrow cells were exposed to a water bath temperature. There were no significant effects of the CFUs with the water bath temperature, while after exposure to microwaves the number of spleen colonies was elevated with a nadir at the temperature of 37 degrees C. With a microwave-induced increase of the temperature above 41 degrees C the number of CFUs in the bone marrow suspension decreased. The increase in the number of colonies was related to the rise in the seeding rate of the CFUs as well as to a rise in their proliferative activity, while the drop in the number of colonies was influenced also by heat-killing of the CFUs by microwave exposure.

Effect of isoprinosine on haemopoietic stem cells (CFU) in bone marrow and spleen of mice.

Peroral application of Isoprinosine for 3, 5 and 10 days increases the number and proliferative activity of haemopoietic stem cells (CFUs) in the bone marrow of mice. Changes in the spleen occur later and are manifested by an increase in CFUs proliferative activity and by a transient decrease in CFUs number.

Increased protective effect of hypoxia against radiation following activation of haemopoiesis with dextran sulphate.

The effect of pretreatment of mice with a single injection of dextran sulphate (DS) on the protective capacity of moderate hypoxia was analysed. Dextran sulphate activated haemopoietic stem cell populations, and irradiation under hypoxia one day after DS injection increased the number of haemopoietic stem cells surviving in the bone marrow of the femur, their recovery after irradiation, and the number of endogenous spleen colonies. A moderate hypoxia (15% O2 and 12% O2) significantly reduced the lethal effect of gamma rays in mice after DS injection and increased the value of LD 50/30.