Structure-functional states of liver mitochondrial membranes of rats exposed to irradiation

The effect of the low dose gamma-irradiation (270 cGy--one-fold; 90 cGy per day during 3 days) on oxidative phosphorylation, lipid peroxidation, microviscosity of the annular and free lipids membrane, and membrane protein structural state was studied. The post-radiation influence on membrane functional activity and structural state in accordance with the irradiation regimes was established.     

DNA-protein cross-links in nuclei and mitochondria of tissue cells from rats of various age exposed to gamma-radiation

The formation and repair of DNA-protein cross-links (DPC) in the mitochondria and nuclei from the brain and spleen of 2- and 29-month rats after their exposure to ionizing radiation were studied. The background level of DPC in brain and spleen mitochondria of old rats was shown to be about two times as high as in young rats. In the nuclei from the brain of old rats the background amount of DPC was also increased, unlike the nuclei of spleen of the same rats. At the doses 5 and 10 Gy (137Cs), the amount of DPC produced in the mitochondria and nuclei of brain and spleen of 29-month rats was 1.8-2.5 times greater than in the nuclei of the same tissues of young animals. At the same time, in the mitochondria of brain and spleen from irradiated rats the amount of DPC was by 30-80% higher than in the nuclei of the same tissues. Analysis of changes in DPC content during the post-radiation period showed that 5 h after irradiation of rats with a dose of 10 Gy, the level of these lesions in the nuclei of brain and spleen of young rats decreased by 40 and 65%, respectively, whereas the amount of these lesions in the mitochondria did not decrease. In this post-radiation period in nuclei of brain and spleen of old rats the amount of DPC decreased by 20-40%, respectively. However, the data on DPC obtained for the mitochondria of brain and spleen from both young and old rats showed that the amount of these lesions did not decrease during the 5 h post-radiation period. These results enable the suggestion that mitochondria do not possess a system of DPC repair. To summarize, ionizing radiation initiates in the nuclei of brain and spleen of old rats more DPC and their repair proceeds slower than in the nuclei of the same tissues of young animals. In the mitochondria of gamma-radiation exposed old rats more DPC are also produced than in young rats but no repair of DPC is observed in both old and young animals within the 5 h post-radiation period.     

Impact of p53 status on heavy-ion radiation-induced micronuclei in circulating erythrocytes

Transgenic mice that differed in their p53 genetic status were exposed to an acute dose of highly charged and energetic (HZE) iron particle radiation. Micronuclei (MN) in two distinct populations of circulating peripheral blood erythrocytes, the immature reticulocytes (RETs) and the mature normochromatic erythrocytes (NCEs), were measured using a simple and efficient flow cytometric procedure. Our results show significant elevation in the frequency of micronucleated RETs (%MN-RETs) at 2 and 3 days post-radiation. At 3 days post-irradiation, the magnitude of the radiation-induced MN-RET was 2.3-fold higher in the irradiated p53 wild-type animals compared to the unirradiated controls, 2.5-fold higher in the p53 hemizygotes and 4.3-fold higher in the p53 nullizygotes. The persistence of this radiation-induced elevation of MN-RETs is dependent on the p53 genetic background of the animal. In the p53 wild-type and p53 hemizygotes, %MN-RETs returned to control levels by 9 days post-radiation. However, elevated levels of %MN-RETs in p53 nullizygous mice persisted beyond 56 days post-radiation. We also observed elevated MN-NCEs in the peripheral circulation after radiation, but the changes in radiation-induced levels of MN-NCEs appear dampened compared to those of the MN-RETs for all three strains of animals. These results suggest that the lack of p53 gene function may play a role in the iron particle radiation-induced genomic instability in stem cell populations in the hematopoietic system.     

Radioprotective Effect of Aminothiol PrC-210 on Irradiated Inner Ear of Guinea Pig

Radiotherapy of individuals suffering with head & neck or brain tumors subserve the risk of sensorineural hearing loss. Here, we evaluated the protective effect of Aminothiol PrC-210 (3-(methyl-amino)-2-((methylamino)methyl)propane-1-thiol) on the irradiated inner ear of guinea pigs. An intra-peritoneal or intra-tympanic dose of PrC-210 was administered prior to receiving a dose of gamma radiation (3000 cGy) to each ear. Auditory Brainstem Responses (ABRs) were recorded one week and two weeks after the radiation and compared with the sham animal group. ABR thresholds of guinea pigs that received an intra-peritoneal dose of PrC-210 were significantly better compared to the non-treated, control animals at one week post-radiation. Morphologic analysis of the inner ear revealed significant inflammation and degeneration of the spiral ganglion in the irradiated animals not treated with PrC-210. In contrast, when treated with PrC-210 the radiation effect and injury to the spiral ganglion was significantly alleviated. PrC-210 had no apparent cytotoxic effect in vivo and did not affect the morphology or count of cochlear hair cells. These findings suggest that aminothiol PrC-210 attenuated radiation-induced cochlea damage for at least one week and protected hearing.     

Specific effect of attenuated strain of Francisella tularensis on the development of radiation induced lesions in experimental animals and effictiveness of antibacterial therapy for lesions induced by radiation combined with virulemt strain of the bacteria

For study of the effects of whole-body gamma-radiation (1 and 4 Gy) on the response of the body to administration of vaccines and virulent strains of tularemia 206 outbred white mice were used. The results of the study shown that the administration of attenuated bacterial cells in 5 days after exposure to radiation (1 and 4 Gy) caused more severe post-radiation effects and the increase in the number of died animals. The severity of the disease was less if mice were vaccinated in 26 days after irradiation (4 Gy). The treatment of tularemia in irradiated mice twith Riphampicin (daily peroral administration, 5 mg/mouse, duration of treatment--7 days) administered in 4 hours after infection was effective and caused high survival of affected mice. The results show effectiveness of the riphampicin treatment of tularemia in the animals exposed to sublethal dose of radiation.     

Elimination from bone marrow of a supplementary population participating in the proliferation of pluripotent hematopoietic stem cells using mouse brain antiserum

Changes in the number of spleen exo-colonies and post-radiation repopulation of hematopoietic organs were studied in recipients upon injection of bone marrow treated with anti-brain serum (ABS) with and without thymocytes on days 9-14. It was shown that on days 9-11 colony formation in mice injected bone marrow treated with ABS was much lower than the control level. However, by day 14 the number of colonies increased drastically as compared to the control. Thymocyte supplementation normalized colony formation at any time of observation. Similar pattern is noted in post-radiation repopulation of spleen and bone marrow of mice injected bone marrow pretreated with ABS with or without thymocytes. It is assumed that ABS inactivates bone marrow cells participating in the regulation of CFUs proliferation.     

An experimental study of the role of prostaglandins in the mechanism of the occurrence of dyspeptic disorders during the primary reaction after body exposure to ionizing radiation at large doses

The experiments with dogs exposed to 100 Gy of accelerated electrons demonstrated a significant role of prostaglandins in the origin of early post-radiation dyspepsia. Their significance for genesis of post-radiation dyspeptic disturbance caused by exposure to superhigh doses becomes clear-cut when a combination of an antiemetic and inhibitors of prostaglandin biosynthesis is used. A study of the effect of dexamethasone, a blocker of arachidonic acid release, and of voltaren, an inhibitor of prostaglandin formation from cyclic endoperoxide, suggests that it would be appropriate to prevent radiation vomiting and diarrhea by inhibiting both of the above stages in prostaglandin biosynthesis.     

Subcutaneous administration of bovine superoxide dismutase protects lungs from radiation-induced lung injury

Abstract

Background. The objective of the present study was to determine whether single administration of the antioxidant enzyme bovine superoxide dismutase (bSOD) after radiation therapy (RT) mitigates development of pulmonary toxicity in rats. Methods. Female F344 rats (n = 60) were divided among six experimental groups: (1) RT, single dose of 21 Gy to the right hemithorax; (2) RT + 5 mg/kg bSOD; (3) RT + 15 mg/kg bSOD; (4) No RT; (5) sham RT + 5 mg/kg bSOD; and (6) sham RT + 15 mg/kg bSOD. A single subcutaneous injection of bSOD (5 or 15 mg/kg) was administered 24 h post-radiation. The effects of bSOD on radiation-induced lung injury were assessed by measurement of body weight, breathing frequency, and histopathological changes. Immunohistochemistry was used to evaluate oxidative stress (8-OHdG⁺, NOX4⁺, nitrotyrosine⁺, and 4HNE⁺ cells), macrophage activation (ED1⁺), and expression of profibrotic transforming growth factor-β or TGF-β in irradiated tissue. Results. Radiation led to an increase in all the evaluated parameters. Treatment with 15 mg/kg bSOD significantly decreased levels of all the evaluated parameters including tissue damage and breathing frequency starting 6 weeks post-radiation. Animals treated with 5 mg/kg bSOD trended toward a suppression of radiation-induced lung damage but did not reach statistical significance. Conclusions. The single application of bSOD (15 mg/kg) ameliorates radiation-induced lung injury through suppression of reactive oxygen species/reactive nitrogen species or ROS/RNS-dependent tissue damage.     

Change in the structure of rat liver mitochondrial membranes under the effect of ionizing radiation

The effect of gamma-irradiation (under 0-10(3) Gy) on the intensity of lipid peroxidation, the microviscosity of annular and free lipids and the polarization of membrane proteins tryptophan fluorescence was studied in the outer and inner mitochondrial membranes. Some specific individual peculiarities of the mitochondrial membranes post-radiation changes were established.     

Hypophysectomy-induced inhibition of augmented acetylcholine responses of the rat bowel following adrenalectomy and/or whole body irradiation

Summary Functional changes in the intestinal responsiveness to a fixed. dose of acetylcholine were studied in muscle strips removed from young adult male rats previously exposed to whole body gamma radiation. In the irradiated rat the responsiveness to a fixed dose of acetylcholine was found to be augmented in the small intestine but not in the colon. Similar motor patterns for the small intestine were found when muscle strips from adrenalectomized rats were studied. Preradiation adrenalectomy further exaggerated the post-radiation sensitivity of the rat small intestine to acetylcholine. Hypophysectomy prior to either adrenalectomy and/or whole body radiation was associated with an absence of augmented small intestinal motor activity following administration of acetylcholine. The response of the large bowel to acetylcholine, however, was not modified by adrenalectomy and/or hypophysectomy. These observations suggest an endocrine component to the acute 3–5 day intestinal radiation syndrome.This work was presented at the 25th Annual Meeting of the Radiation Research Society, San Juan, Puerto Rico, May 1977     

Localized Intestinal Radiation and Liquid Diet Enhance Survival and Permit Evaluation of Long-Term Intestinal Responses to High Dose Radiation in Mice

Background

In vivo studies of high dose radiation-induced crypt and intestinal stem cell (ISC) loss and subsequent regeneration are typically restricted to 5–8 days after radiation due to high mortality and immune failure. This study aimed to develop murine radiation models of complete crypt loss that permit longer-term studies of ISC and crypt regeneration, repair and normalization of the intestinal epithelium.

Methods

In C57Bl/6J mice, a predetermined small intestinal segment was exteriorized and exposed to 14Gy-radiation, while a lead shield protected the rest of the body from radiation. Sham controls had segment exteriorization but no radiation. Results were compared to C57Bl/6J mice given 14 Gy-abdominal radiation. Effects of elemental liquid diet feeding from the day prior to radiation until day 7 post-radiation were assessed in both models. Body weight and a custom-developed health score was assessed every day until day 21 post-radiation. Intestine was assessed histologically.

Results

At day 3 after segment radiation, complete loss of crypts occurred in the targeted segment, while adjacent and remaining intestine in segment-radiated mice, and entire intestine of sham controls, showed no detectable epithelial damage. Liquid diet feeding was required for survival of mice after segment radiation. Liquid diet significantly improved survival, body weight recovery and normalization of intestinal epithelium after abdominal radiation. Mice given segment radiation combined with liquid diet feeding showed minimal body weight loss, increased food intake and enhanced health score.

Conclusions

The segment radiation method provides a useful model to study ISC/crypt loss and long-term crypt regeneration and epithelial repair, and may be valuable for future application to ISC transplantation or to genetic mutants that would not otherwise survive radiation doses that lead to complete crypt loss. Liquid diet is a simple intervention that improves survival and facilitates long-term studies of intestine in mice after high dose abdominal or segment radiation.     

Reduction of radiation-induced nitrative stress in leucocytes and kidney cells of rats upon administration of polyphenolic complex concentrates from red wine

The research has shown that exposure to ionizing radiation at the dose of 30 cGy leads to the activation of NO-synthase way of nitrogen oxide synthesis, as well as to the accumulation of its stable metabolites and 3'-nitrotyrosine modified proteins in rat peripheral blood leucocytes and the renal cortical layer. NO-synthase activity was preserved at the control value through the consumption of red wine naturalpolyphenolic complex concentrates by the irradiated animals. The content of proteins modified by tyrosine nitration decreased in the early period of post-radiation exposure due to the influence of the investigated concentrate. Thus the ability of red wine natural polyphenolic complex concentrates to prevent adverse changes in L-arginine/NO system and, therefore, inhibit the development of nitrative stress induced by low doses of ionizing radiation has been proved experimentally.     

Cardiovascular Changes in Atherosclerotic ApoE-Deficient Mice Exposed to Co60 (γ) Radiation

Background

There is evidence for a role of ionizing radiation in cardiovascular diseases. The goal of this work was to identify changes in oxidative and nitrative stress pathways and the status of the endothelinergic system during progression of atherosclerosis in ApoE-deficient mice after single and repeated exposure to ionizing radiation.

Methods and Results

B6.129P2-ApoE tmlUnc mice on a low-fat diet were acutely exposed (whole body) to Co60 (γ) (single dose 0, 0.5, and 2 Gy) at a dose rate of 36.32 cGy/min, or repeatedly (cumulative dose 0 and 2 Gy) at a dose-rate of 0.1 cGy/min for 5 d/wk, over a period of 4 weeks. Biological endpoints were investigated after 3–6 months of recovery post-radiation. The nitrative stress marker 3-nitrotyrosine and the vasoregulator peptides endothelin-1 and endothelin-3 in plasma were increased (p<0.05) in a dose-dependent manner 3–6 months after acute or chronic exposure to radiation. The oxidative stress marker 8-isoprostane was not affected by radiation, while plasma 8-hydroxydeoxyguanosine and L-3,4-dihydroxyphenylalanine decreased (p<0.05) after treatment. At 2Gy radiation dose, serum cholesterol was increased (p = 0.008) relative to controls. Percent lesion area increased (p = 0.005) with age of animal, but not with radiation treatment.

Conclusions

Our observations are consistent with persistent nitrative stress and activation of the endothelinergic system in ApoE−/− mice after low-level ionizing radiation exposures. These mechanisms are known factors in the progression of atherosclerosis and other cardiovascular diseases.     

Radiation and platinum drug interaction

Platinum drugs have chemical as well as biochemical and biological effects on cells, all of which may interact with radiation effects. They inhibit recovery from sublethal and potentially lethal radiation damage. They produce a pattern of chromosome aberrations analogous to that from alkylating agents. Cellular sensitivity to platinum is increased when glutathione levels are reduced, just as is radiosensitivity. There is a pattern of drug sensitivity throughout the phases of the cell cycle which is different from that for radiosensitivity. The ideal platinum drug-radiation interaction would achieve radiosensitization of hypoxic tumour cells with the use of a dose of drug which is completely non-toxic to normal tissues. Electron-affinic agents are employed with this aim, but the commoner platinum drugs are only weakly electron-affinic. They do have a quasi-alkylating action however, and this DNA targeting may account for the radiosensitizing effect which occurs with both pre- and post-radiation treatments. Because toxic drug dosage is usually required for this, the evidence of the biological responses to the drug and to the radiation, as well as to the combination, requires critical analysis before any claim of true enhancement, rather than simple additivity, can be accepted. The amount of enhancement will vary with both the platinum drug dose and the time interval between drug administration and radiation. Clinical schedules may produce an increase in tumour response and/or morbidity, depending upon such dose and time relationships.     

A mathematical model of the course of the DNA synthesis in mammalian cells after ultraviolet irradiation and its use in the determination of the length of the replicon

The chromosome of mammalian cells is divided into several shorter segments — replicons which replicate separately. When the cells are irradiated with ultraviolet radiation the pyrimidine flimers preventing the DNA-polymerase in its normal function and creating obstacles for a timely completing of the implication are formed. Using these facts as a basis we have derived a mathematical model of the course of the DNA synthesis in mammalian cells after ultraviolet irradiation, it has been proved that for the determination of the average length of units of replication in chromosomes of these cells the measurement of the intensity of post-radiation DNA synthesis in an asynchronous culture of mammalian cells can be used. Directions for the determination of this length using results of the measurement of the post-radiation synthesis are given, too. The whole method has already beer, tested on mammalian L-cells.     

Potential alternative treatment approach for pediatric patient with diffusely infiltrative primary rhabdomyosarcoma of the liver

Primary hepatic rhabdomyosarcoma is rare, making decisions regarding locoregional management with resection and/or conventional radiation difficult. We present a novel treatment approach for a pediatric patient diagnosed with rhabdomyosarcoma diffusely involving the liver. This patient underwent treatment with yttrium-90 (Y-90) microspheres followed by external beam radiation therapy (EBRT ) to residual disease, interdigitated with systemic chemotherapy. Initial post-radiation imaging showed significant response to treatment, and she experienced minimal acute toxicities and no long-term toxicities. She developed recurrent PET-avid disease 23 months after Y-90 treatment, necessitating further local and continued systemic therapies. We report on the tumor control following Y-90 and EBRT treatment.     

Prognosis of Post-Radiation Dynamics of Blood Neutrophil Count in Cases of Acute Uneven Irradiation (Cytogenetic Studies)

Biology Bulletin - The results of applying the method of prognosis of post-radiation curves of neutrophil count dynamics in the blood after acute nonuniform human irradiation based on the use of a...     

Should we affraid of induced cancer in group of patients after radical radiotherapy of prostate cancer?

Radiotherapy is one of the basic methods of radical treatment of prostate cancer. Because of that getting to know all factors of post-radiation complications, and in consequence the possibility to limit them, is one of the challenges of contemporary radiotherapy.One of the potential complications associated with radiation treatment is radiation-induced cancer. Despite a whole range of epidemiological analyses there is still lacking a fully credible model that would allow one to estimate the magnitude of risk of inducing such cancers. The last decades have seen the entry into clinical practice of technologically advanced methods of radiation therapy, such as the 3DCRT and IMRT. As the previous epidemiological analyses refer mainly to older radiation techniques, there is still a lack of credible data estimating the risk of inducing secondary cancers for new techniques, and in particular IMRT. It should be emphasized that IMRT allows one to escalate the dose, which may contribute to the improvement of radiotherapy effectiveness. From this there follows a new problem to be solved in future, i.e. how the escalation of the dose may influence the magnitude of risk of radiation carcinogenesis.The problem of carcinogenesis may concern the group of younger patients for whom long survival is very likely, and the competitive edge of RT relative to surgery, in particular in the aspect of late complications, has to be thoroughly justified.     

Effect of radiation-induced bystander chemosignals of mice on the humoral immune response in spleen and lymph nodes of intact recipients

The ability of post-radiation (4 Gy) bystander chemosignals (the volatile components of mouse urine) to distantly modulate the humoral immune response to the sheep red blood cells in the spleen and popliteal lymph nodes of intact recipients has been investigated. It was shown that the exposure of animals to chemosignals before antigen injection resulted in the decrease and increase of the immune response in the spleen and lymph nodes, respectively. When animals were exposed to chemosignals after the antigenic stimulus, an increased immune response was observed in both spleen and lymph nodes. The contribution of radiation-induced bystander signaling in the response of socially organized animals to the effect of ionizing irradiation is discussed.