Are the changes in collagen caused by chronical X-irradiation similar to aging?

It has been shown that in the skin of chronically irradiated rats the proportion of collagen type III as compared to collagen type I is increased; on the other hand, no changes in the overall proportion to collagen were observed in the skin. It appears that the increased proportion of collagen type III in chronically irradiated rats is responsible for the decreased solubility of cutaneous collagen in these animals. Concomitantly, indirect evidence was accumulated for the presence of an additional cross-link in type III collagen, present only when irradiated animals served as the collagen source. This cross-link is located subterminally as long as it is not removed by limited pepsin digestion. It was concluded that the physiological decrease in solubility and the decrease in solubility observed in chronically irradiated animals have a different molecular background.     

Modulatory effect of Mentha piperita (Linn.) on serum phosphatases activity in Swiss albino mice against gamma irradiation

Mentha extract (ME; 1 g/kg body wt) given orally for three consecutive days prior to whole body irradiation (8 Gy) showed modulation of activity of serum phosphatases in albino mice. Values of acid phosphatase activities were significantly higher in untreated irradiated group throughout the experiment. Irradiated animals pretreated with ME showed significant decline in acid phosphatase activity as compared to untreated irradiated animals at all autopsy intervals and attained normalcy at day 5. A marked decrease in serum alkaline phosphatase activity was recorded in both irradiated groups. However, in ME pretreated irradiated group, values of alkaline phosphatase activity remained significantly higher than untreated irradiated animals at all intervals and attained normalcy from day 5 onwards.     

Influence of protein nutrition on dose-survival relationship following rat kidney irradiation

Immediately following unilateral nephrectomy the remaining kidney of juvenile male Sprague-Dawley rats was sham irradiated or irradiated to doses of 14-30 Gy. Following irradiation the animals were placed on isocaloric diets of either 20 or 4% protein. Median life spans for the animals on the low protein diet were significantly increased compared to the median life spans on the 20% protein diet. Serum urea nitrogen (SUN) levels were periodically measured in rats from each of the experimental groups. SUN levels in the irradiated rats fed the 20% protein diet increased significantly over unirradiated controls as a function of time. In contrast animals fed the 4% protein diet showed no significant changes in SUN levels irrespective of the size of radiation dose and time post irradiation. Renal protective factors calculated as the ratio of 80% survival times for animals fed the 20% protein diet compared to animals fed the 4% protein diet can be calculated to be 2.3 at 18 Gy and 2.8 at 22 Gy. Likewise, a SUN protective factor calculated as the ratio of percentage of nonirradiated control SUN values for the two diets (SUN 20% irradiated) (SUN 20% nonirradiated) (SUN 4% irradiated) (SUN 4% nonirradiated) is 2.4 for 18 Gy and 3.9 for 22 Gy.     

Possible involvement of L-type voltage-gated calcium channels in release of dopamine in the striatum of irradiated rats

The object of this study was to determine the effect of exposure to gamma radiation on potassium chloride (KCl)-stimulated release of dopamine (DA) in the striatum of the rat. In addition, the effect of some calcium channel blockers [nicardipine, a blocker of the L-type voltage-gated N-type VGCC; Omega-agatoxin TK, a selective blocker of P-type VGCC; and nickel chloride (NiCl(2)), which preferentially blocks the T-type VGCC] on KCl-stimulated release of DA in the striatum in sham-irradiated and irradiated rats was determined. Exposure of rats to 1-10 Gy (60)Co gamma rays had no significant effect on KCl-stimulated release of DA in the striatum in comparison to sham-irradiated animals. Administering 100, 300 and 500 nM of Omega-agatoxin TK or 50, 100 and 200 nM of Omega-conotoxin GVIA significantly decreased the release of DA stimulated by KCl in both irradiated and sham-irradiated animals in a dose-dependent manner. However, 10, 30 and 50 microM of nicardipine decreased the release of DA in irradiated animals but not in sham-irradiated animals. It is unknown why doses of 5-20 microM NiCl(2) had no effect on the release of DA in sham-irradiated and irradiated animals. The results demonstrate that the doses of radiation used in this study had no effect on release of DA in the striatum. Multiple calcium channel types coexist to regulate release of DA. P- and N-type VGCCs are involved in release of DA in sham-irradiated and irradiated animals, whereas only L-type VGCCs are involved in release of DA in irradiated animals.     

The influence of aromatic amino acid derivatives on the complement system under ionizing radiation

The activities of the complement classical, alternative, and lectin pathways are determined under conditions of X-ray irradiation in the blood of rats treated and not treated with synthetic Schiff base aromatic amino acid derivatives, nicotinyl-L-tyrosinate or nicotinyl-L-tryptophanate, before irradiation. In the case of the activities of the alternative and lectin pathways, no significant changes between irradiated animals and non-irradiated control animals are detected. However, the data obtained demonstrate significantly elevated activity of the classical complement cascade in the blood of irradiated animals (one day after irradiation), as compared to those not irradiated. This effect is less pronounced in rats treated with nicotinyl-L-tyrosinate or nicotinyl-L-tryptophanate one hour before irradiation. Based on the results obtained, we conclude that nicotinyl-L-tyrosinate and nicotinyl-L-tryptophanate are able to act as cytoprotectors.     

Effect of irradiation on the in vivo and in vitro subcellular distribution of radiostrontium in rat liver

Hepatic mitochondrial strontium uptake is enhanced in whole body irradiated rats. Effect is observed on animals but not on irradiated organ slices. It is likely that a hypophyso - adrenal axis hormone plays a role in changes observed in vivo.     

Dose rate and oxygen consumption rate in mice confined in a small holder during exposure to 2450 MHz microwave radiation

Summary The average dose rate and oxygen consumption rate of an individual mouse in a small holder during exposure to 2450 MHz CW microwave radiation are determined. The environmental conditions are 24° C temperature, 55% relative humidity, and 78 ml/min airflow. A forward power of 1.7 W resulted in the average dose rates of 31.0 mW/g, and 23.6 mW/g respectively, for the animals irradiated in the small, and the large holders. The results support the hypothesis that previously observed reduction in microwave energy absorption during irradiation is due to the orientation and positioning of the animal's body with respect to the microwave field. Relatively higher rate of oxygen consumption of the tightly confined sham-irradiated animals in comparison to that of the animals in the large holder is observed. Although a decrease in oxygen consumption rate is observed during exposure for the microwave irradiated animals in the small holder, the magnitude of this decrease is not more than that of the animals irradiated in the large holder. Thus the lack of reduction in the absorption of microwave energy is not compensated by a correspondingly large decrease in oxygen consumption, resulting in a larger heat load and perhaps larger stress to animals confined in the small holder.     

On the Wholesomeness of γ-Irradiated Potatoes

Fattening pigs and pigs for breeding have been fed γ-irradiated and non-irradiated control potatoes. The irradiation dose was 14–15 kilorad at the rates 175 r/sec. and 625 r/hr. Rats (Wistar) were also fed irradiated and control potatoes, but in this case the tubers were given a dose of about 200 kilorad. No unfavourable effects have been observed from the feeding with irradiated potatoes. All the facts indicate that the nutritional adequacy of the irradiated and the control tubers is equal. In some cases, the animals have even shown an improvement after feeding on irradiated potatoes which was not apparent after feeding on non-irradiated potatoes; for example there was a more rapid growth, somewhat higher fertility, and increased haemoglobin values. However, current experiments with larger groups of animals will provide more definite evidence in these questions.     

Effect of ionizing radiation on the protein-synthesizing system of brain neurons of ground squirrels in different functional states

Using fluorescence and electron microscopy, it is shown that the physiological state of ground squirrels exposed to ionizing radiation at different stages of the torpor-awakeness (hypothermia-normothermia) cycle is the main factor responsible for changes in the protein-synthesizing system of neurons in the hippocampus (fields CA1 and CA3) and the sensomotor cortex. The neurons of animals irradiated in the state of awakeness are less radioresistant and recover more slowly than neurons of animals irradiated in torpor, with the difference being more distinct in neurons of the CA1 field. The effect of irradiation is weak in animals entering torpor and reaches a peak in awakening animals. It is proposed that the inhibition of protein synthesis in the latter case takes place at the elongation stage, with heavy polysomes formed in the cytoplasm of neurons.     

Irradiation potentiation of cellular transfer of EAE: time course and locus of effect in irradiated recipient Lewis rats.

Further studies of the potentiating effect of 500 rads total body irradiation on cellular transfer of experimental allergic encephalomyeliatis (EAE) in Lewis rats have revealed two findings bearing on underlying mechanisms. First, the effect is transitory, potentiation of disease being observed in recipients irradiated 1 or 4 days before transfer of syngeneic sensitized donor lymphoid cells but not among animals irradiated 7 or 14 days before cell transfer. Second, lead shielding selectively excluding the central neuraxis from irradiation results in relatively little augmentation of EAE compared to that observed in non-shielded irradiated animals. We believe irradiation potentiation of EAE results from transitory alterations in central nervous system target tissue rendering it more vulnerable to host immunologic attack.     

Role of the Phagocyte in Host-Parasite Interactions VIII. Effect of Whole-Body X Irradiation on Nicotinamides, Lysosomal Enzymes, and Bactericidal Activities of Leukocytes During Phagocytosis

By studying the effects of whole-body X irradiation on phagocytosis, a correlation between the metabolic and bactericidal activities of leukocytes following X irradiation was demonstrated. The total nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) content of polymorphonuclear neutrolphils (PMN) isolated from irradiated guinea pigs increased significantly when compared to nonirradiated controls. The ratio of unreduced to reduced (NAD) generally increased in PMN isolated from irradiated animals. This occurred with both resting and phagocytizing cells. The ratio of unreduced to reduced NADP of resting PMN isolated from irradiated animals had a tendency to increase. However, in phagocytizing cells a significant decrease in the ratio was noted. The total acid and alkaline phosphatase and beta-glucuronidase increased up to about 10 days postirradiation. These lysosomal enzymes returned to approximately normal by the 17th day postirradiation. All three lysosomal enzymes (acid and alkaline phosphatases and beta-glucuronidase) were released from the granules at a significantly faster rate during phagocytosis after irradiation. The bactericidal activities of PMN isolated from irradiated animals gradually decreased, and in some cases increased growth of the organisms was observed. The uptake or association of bacteria with PMN isolated from irradiated animals varied with the postirradiation time. Generally, a correlation with bactericidal activities could be made. The data indicate that the bactericidal system in phagocytes consists of at least two agents, H(2)O(2) and myeloperoxidase.     

Effect of herbal preparation, brahma rasayana, in amelioration of radiation induced damage

Oral administration of brahma rasayana (BR; 10 and 50 mg/dose/animal) for 15 days increased significantly total leukocyte count and percentage of polymorphonuclear cells in irradiated mice. Bone marrow cellularity and alpha-esterase positive cells also increased significantly in radiation-treated animals after BR administration. Number of nodular colonies on the surface of spleen on day seven increased significantly in lethally irradiated recipients receiving bone marrow cells from animals treated with BR. Oral administration of BR also enhanced in serum level of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and granulocyte macrophage-colony stimulating factor(GM-CSF) in normal and irradiated mice. These results indicated that proliferation of stem cells induced by BR in irradiated mice may be related to its stimulation of cytokine production.     

The effect of total gnotobiological isolation and antimicrobial preparations on the survival of mice with acute radiation sickness

In experiments on 406 CBA mice the effect of antimicrobial preparations, used in combination with total gnotobiotic isolation, on the survival rate of totally irradiated animals was studied. The use of antimicrobial preparations was shown to considerably enhance the survival rate of these animals. Cyprofloxacin, a new preparation of the kinolone row, exhibited a good effect ensuring selective decontamination of the intestine. The use of cyprofloxacin prior to irradiation with the subsequent isolation of the animals in gnotobiotic chambers increased the survival rate of these animals by 2.7 times. But the maximum survival rate of irradiated mice was observed in those cases when antimicrobial preparations were used both before and after irradiation in combination with the total gnotobiotic isolation of the animals.     

The effect of a mammalian repair endonuclease on x-irradiated DNA.

DNA was extracted from rat liver of non-irradiated animals, and was irradiated in vitro, and from animals which received whole body doses of X-radiation. Sedimentation on neutral and alkaline sucrose gradients as well as measurements of 32P release after sequential treatment with endonuclease and alkaline phosphatase and determination of triphosphate incorporation after the sequential treatment with endonuclease, alkaline phosphatase and DNA polymerase indicated that DNA irradiated in vivo and in vitro were effective substrates for the mammalian repair endonuclease. The experiments suggest that in addition to strand breaks, X-radiation causes base damage and they have provided a plausible explanation for the formation of double strand breaks in DNA irradiated in vivo.     

The influence of gamma-irradiation and alimentry factors on prooxidant-antioxidant rat's liver and blood system

The shift of prooxidant-antioxidant balance in side of prooxidants was revealed in rat liver mitochondria and in microsomes and in blood plasma in response to single irradiation (dose 8 Gy). The shift was more expressed in animals with nutrition unbalanced on animal proteins and antioxidant vitamins. In the main it was explained by the initially reduced activity of enzymatic antioxidant system and especially Se-dependent glutathione peroxidase activity. The apply of food addition from Aronia melanocarpa fruits had delayed lipid peroxidation activation in irradiated animals but practically had no effect on activity of enzymatic antioxidant system. The established essential decrease of Se-dependent glutathione peroxidase activity under unbalanced diet is considered the most crucial point in the maintenance of enzymatic antioxidant system reliability in irradiated animals.     

The influence of aromatic amino acid derivatives on the complement system under ionizing radiation

Activities of the complement classical, alternative and lectin pathways were determined under conditions of X-radiation in the blood of rats treated and none-treated with synthetic Schiffbase aromatic amino acid derivatives, nicotinyl-L-tyrosinate or nicotinyl-L-tryptophanate, before irradiation. In case of activities of the alternative and lectin pathways no significant changes between irradiated animals and none-irradiated control animals were detected. However, the data obtained demonstrate significantly elevated activity of the classical complement cascade in the blood of irradiated animals (1 day after irradiation), as compared to those none-irradiated. This effect was less pronounced in rats treated with nicotinyl-L-tyrosinate or nicotinyl-L-tryptophanate 1 hour before irradiation. Based on the results obtained the ability of nicotinyl-L-tyrosinate and nicotinyl-L-tryptophanate to act as cyto-protectors is concluded.     

Use of synchrotron medical microbeam irradiation to investigate radiation-induced bystander and abscopal effects in vivo

The question of whether bystander and abscopal effects are the same is unclear. Our experimental system enables us to address this question by allowing irradiated organisms to partner with unexposed individuals. Organs from both animals and appropriate sham and scatter dose controls are tested for expression of several endpoints such as calcium flux, role of 5HT, reporter assay cell death and proteomic profile. The results show that membrane related functions of calcium and 5HT are critical for true bystander effect expression. Our original inter-animal experiments used fish species whole body irradiated with low doses of X-rays, which prevented us from addressing the abscopal effect question. Data which are much more relevant in radiotherapy are now available for rats which received high dose local irradiation to the implanted right brain glioma. The data were generated using quasi-parallel microbeams at the biomedical beamline at the European Synchrotron Radiation Facility in Grenoble France. This means we can directly compare abscopal and “true” bystander effects in a rodent tumour model. Analysis of right brain hemisphere, left brain and urinary bladder in the directly irradiated animals and their unirradiated partners strongly suggests that bystander effects (in partner animals) are not the same as abscopal effects (in the irradiated animal). Furthermore, the presence of a tumour in the right brain alters the magnitude of both abscopal and bystander effects in the tissues from the directly irradiated animal and in the unirradiated partners which did not contain tumours, meaning the type of signal was different.     

Interleukin 4 promotes survival of lethally irradiated mice in the absence of hematopoietic efficacy

The therapeutic potential of Il4 in lethally irradiated mice was evaluated in C57BL6/J mice subjected to 7 to 10 Gy total-body irradiation (TBI) from a (60)Co gamma-ray source. Il4 was administered 2 h after TBI either in a single injection or for 5 consecutive days. Il4 treatment increased 30-day survival of mice irradiated with doses as high as 8.5 Gy, which caused 100% mortality in placebo-treated animals. By convention, hematopoietic failure would induce death over a period of up to 30 days. However, in our study, the Il4-enhanced survival of mice within this period could not be attributed to significantly accelerated hematopoietic reconstitution as shown by blood cell counts and progenitor cell contents in the bone marrow and spleen. Our data strongly suggest that aplasia is not the only cause of death of animals irradiated with doses around the LD(50) and that Il4-treated animals can survive in spite of a very poor hematopoietic activity.     

Cardiac endothelial cells isolated from mouse heart - a novel model for radiobiology

Cardiovascular disease is recognized as an important clinical problem in radiotherapy and radiation protection. However, only few radiobiological models relevant for assessment of cardiotoxic effects of ionizing radiation are available. Here we describe the isolation of mouse primary cardiac endothelial cells, a possible target for cardiotoxic effects of radiation. Cells isolated from hearts of juvenile mice were cultured and irradiated in vitro. In addition, cells isolated from hearts of locally irradiated adult animals (up to 6 days after irradiation) were tested. A dose-dependent formation of histone γH2A.X foci was observed after in vitro irradiation of cultured cells. However, such cells were resistant to radiation-induced apoptosis. Increased levels of actin stress fibres were observed in the cytoplasm of cardiac endothelial cells irradiated in vitro or isolated from irradiated animals. A high dose of 16 Gy did not increase permeability to Dextran in monolayers formed by endothelial cells. Up-regulated expression of Vcam1, Sele and Hsp70i genes was detected after irradiation in vitro and in cells isolated few days after irradiation in vivo. The increased level of actin stress fibres and enhanced expression of stress-response genes in irradiated endothelial cells are potentially involved in cardiotoxic effects of ionizing radiation.