Highly activated carbon enterosorbent mediates the suppression of paraneoplastic syndrome associated with Lewis lung carcinoma in mice.

AIM: To investigate the effect of enterosorption on the development of paraneoplastic syndrome in mice with Lewis lung carcinoma (LLC). MATERIALS AND METHODS: The study was performed on male С57/ВL6 mice with transplanted LLC. As an enterosorbent, highly activated powder fraction of HSGD was administered per os daily at a dose of 0.625 g/kg for two weeks starting from the 7th day after tumor cell transplantation. Analysis of hemo- and myelograms, morphological alterations in vital organs, the activities of catalase and superoxide dismutase, biochemical analysis of blood and quantitative analysis of hydroperoxides, malonic dialdehyde, аdvanced oxidation protein products was carried out by standard methods after completing the course of enterosorption. Ligand loading of blood plasma proteins was estimated by the method of differential scanning microcalorimetry. RESULTS: Administration of enterosorbent resulted in inhibition of LLC growth and in nearly 2-fold decrease of lung metastases number (p < 0.05). Activation of granulocytic line in the bone marrow with nearly 3-fold enhancement of mitotic activity took place after enterosorbent administration. Red cell lineage indices and bone marrow cellularity remained unaltered. After enterosorption session, the studied biochemical indices of peripheral blood evidenced on decreasing the endogenous intoxication and oxidative stress levels, improving the functional state of kidneys, increasing the resistance of erythrocyte membranes and lowering the ligand loading of blood plasma transport proteins. Morphological structure of kidneys and liver confirmed significant positive effect of enterosorption. The data of morphologic examination of gastric fundus, small intestine, and large bowel slides after 2-week administration of enterosorbent showed its high safety and proper evacuation from intestine. CONCLUSION: The two-week long enterosorption session in mice with LLC caused the suppression of tumor growth and metastasis, normalization of bone marrow hemopoiesis. Enterosorption exerted a positive influence on the structural-morphologic indexes and regenerative potential of kidneys and liver, mitigated manifestations of oxidative stress, decreased the level of endogenous intoxication, promoted deliganding of albumin molecule and deloading of erythrocyte membranes.

Mesenchymal stem and progenitor cells of rats' bone marrow under chronic action of ionizing radiation. / MEZENKhIMAL'NI STOVBUROVI KLITYNY TA KLITYNY POPEREDNYKY KISTKOVOGO MOZKU ShchURIV V UMOVAKh KhRONIChNOÏ DIÏ IONIZUIuChOÏ RADIATsIÏ.

Under the influence of ionizing radiation on hematopoietic system, the level of its injury is determined not only by the radiosensitivity of hematopoietic stem cells, but also by radiation induced changes in microenvironment func tioning, in particular, mesenchymal stem cells as its components. OBJECTIVE: to define functioning characteristics of mesenchymal stem and progenitor cells of rats' bone marrow under prolonged action of ionizing radiation as a result of 90Sr incorporation. MATERIALS AND METHODS: We applied the model of Wistar rats' internal irradiation with 90Sr radionuclide and per formed the in vitro cultivation of their bone marrow mesenchymal cells. Colony forming efficiency in the in vitro cell culture was determined, as well as the possibility of these cells to form feeder layers and to support rat bone mar row hematopoietic cells in the culture of diffusion chambers in vitro. RESULTS AND CONCLUSIONS: We established that chronic action of incorporated 90Sr radionuclide induced considerable decrease in proliferative activity of mesenchymal stem cells comparing to control, as well as the inhibition of the capability to prolonged support of hematopoietic processes in vitro by their feeder layers.Thus, bone marrow mesenchymal stem cells and their closest progeny - progenitor cells were characterized by rather high radiosensitivity under the influence of ionizing radiation, which was revealed in considerable decline of their functional activity in cell culture in vitro comparing to control indices as a result of irradiation.

Transgeneration effects of N-stearoylethanolamine in irradiated rats. / TRANSGENERATsIY̆NI EFEKTY N-STEAROÏLETANOLAMINU V OPROMINENYKh ShchURIV.

OBJECTIVE: to explore possible transgeneration effects in the rats offspring of the first generation of parents subject ed to the combined effects of N stearoylethanolamine (NSE) and external exposure.Materials and metods. In the first generation rats of both sexes born to parents who have experienced the combined influence of ionizing radiation at a dose of 2.0 Gy and NSE a daily dose of 50.0 mg/kg, administered before or after exposure indicators of pro and antioxidant systems (the concentration of TBA reactive products, catalase and glu tathione peroxidase activity in plasma) were defined, concentrations of sex hormones testosterone and estradiol and nitrite anion were studied. RESULTS: Irradiation of parents caused a three fold reduction of testosterone in the blood plasma of males progeny, increased activity of catalase in plasma of female offsprings, as well as significantly increased the concentration of protein in the offsprings' blood plasma of both sexes. Introduction of NSE to parents before exposure caused the acti vation of lipid peroxidation in plasma of both sexes offsprings' against the background of a trustworthy decrease in activity of antioxidant enzymes (catalase and glutathione peroxidase), however, prevented a sharp reduction of testosterone content in the blood plasma of males offsprings, conditioned by the influence of radiation on the body of their parents. NSE introduction to parents after exposure caused no significant violations of pro/ antioxidant bal ance in the body of both sexes progeny, but did not eliminate the negative impact of parental exposure to testos terone levels in male offsprings. CONCLUSION: The transgeneration impact of NSE is manifested by radio sensitizing properties in the first generation offsprings in case of application to parents before irradiation.

Pattern changes in quantitative and qualitative markers of hematopoietic stem cells during acute and chronic exposure to 90Sr isotope in cell culture. / ZAKONOMIRNOSTI ZMIN KIL'KISNYKh I IaKISNYKh POKAZNYKIV GEMOPOETYChNYKh STOVBUROVYKh KLITYN U KUL'TURI KLITYN V UMOVAKh DIi RADIONUKLIDU STRONTsIIu-90.

OBJECTIVE: The objective of our research was investigation of the hematopoietic system of laboratory rats under the influence of acute and chronic internal exposure to 90Sr isotope. MATERIALS AND METHODS: To study the condition of stem cells and their immediate progenitors we implemented cell culture methodology in vivo in gel diffusion capsules with subsequent analysis of the colonies and clusters. RESULTS: On the basis of experiments it was established that long-term effects of incorporated 90Sr isotope leads to significant disturbances in the hematopoietic system and in particular, revealing changes in hematological parameters of irradiated animals such as the appearance of circulating progenitor cells in peripheral blood, reducing the colony-forming efficiency of the bone marrow derived progenitor cells, as well as quantitative and qualitative changes in the clones. CONCLUSIONS: Indices confirm the connection of the detected effects in individuals exposed to ionizing radiation described in the earlier publications and can serve as basis for developing criteria for the formation of risk groups among people exposed to 90Sr.

Overview on association of different types of leukemias with radiation exposure.

Exposure to ionizing radiation is associated with increasing risk of various types of hematological malignancies. The results of major studies on association of leukemias and radiation exposure of large populations in Japan and in Ukraine are analyzed. The patterns of different types of leukemia in 295 Chernobyl clean-up workers diagnosed according to the criteria of up-to-date World Health Organization classification within 10-25 years following Chernobyl catastrophe are summarized. In fact, a broad spectrum of radiation-related hematological malignancies has been revealed both in Life Span Study in Japan and in study of Chernobyl clean-up workers in Ukraine. The importance of the precise diagnosis of tumors of hematopoietic and lymphoid tissues according to up-to-date classifications for elucidating the role of radiation as a causative factor of leukemias is emphasized. Such studies are of high importance since according to the recent findings, radiation-associated excess risks of several types of leukemias seem to persist throughout the follow-up period up to 55 years after the radiation exposure.

Fractionated low-dose radiation exposure potentiates proliferation of implanted tumor cells.

AIM: The purpose of this study is to test whether whole-body fractionated exposure of tumor-free animals to low doses of low-LET radiation (at the total delivered dose of 1.0 Gy of X-rays) is capable of potentiating growth of subsequently implanted tumor cells. MATERIALS AND METHODS: Adult male rats were fractionally exposed to low doses of X-rays (10 acute exposures with 0.1 Gy each and with a frequency of 1 exposure per 3 days). The next day after the last irradiation rats were implanted with Guerin carcinoma (GC) cells. On the 12th and 18th days after implantation of GC cells, animals were sacrificed, and the mass of tumors was measured by weighing them, although the kinetics of tumor growth was also examined by daily measurements of the dimensions of tumors. Cytotoxic effects in the bone marrow were assessed flow cytometrically in acridine orange-stained unfractionated bone marrow cells using the ratio of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE). RESULTS: In irradiated rats, tumors grew apparently faster than in unirradiated rats for up to 18 days after implantation of GC cells. On the 18th day after implantation of GC cells the average value of the mass of tumors in irradiated rats was 2.8-fold higher compared with the average value of the mass of tumors in unirradiated rats (p < 0.05). On this day post-implantation, the bone marrow in irradiated animals was 1.8-fold more suppressed (as evidenced by decreased PCE/NCE ratios) than that in animals that were irradiated, but were not implanted with GC cells (p > 0.05), and was 1.4-fold more suppressed than that in animals that were not irradiated, but were implanted with GC cells (p > 0.05). CONCLUSION: Fractionated irradiation of tumor-free animals with low doses of X-rays potentiates proliferation of subsequently implanted GC cells. This potentiation seems to be associated with radiation-induced impaired hematopoiesis.

[Genotoxic effects of radiation and hyperthermia in inbred mice strains with different radiation sensitivity].

Peculiarities of repair of DNA injuries induced by radiation and hyperthermia and their realization on chromosomal level in bone marrow cells ofexperimental animals with different radiation sensitivity were studied. It is shown that radiomodification efficiency of mild hyperthermia is higher for radioresistant animals. More intensive elimination of chromosomal injuries the level of which in remote terms of examination corresponds to the control value, is observed. In the group of animals with higher radiation sensitivity prolonged thermal potentiation of radiation effects on chromosomal level is determined.

Combined effect of N-stearoyiletanolamine and ionizing radiation on hematological indices of peripheral blood in rats.

UNLABELLED: The study objective was to explore the peculiarities of peripheral blood values in rats under the combined influence of 10.0 mg/kg N-stearoylethanolamine (NSE) and 6.0 Gy dose of ionizing radiation to identify the radiomodifying properties of the drug. METHODS: hematological, statistical. RESULTS: it was found that NSE injection to irradiated rats leads to exacerbation of hematopoietic system disorders indicating to radiosensitizing effect of the substance. CONCLUSIONS: The radiosensitizing effect of the drug was established according to qualitative and quantitative abnormalities in peripheral blood values of the rats. Effect of the NSE drug on the rate of recovery processes (i.e. retardation) in the peripheral blood of rats after irradiation was established under these experimental conditions.

[Non-specific stress-reaction as indicator of radiosensitivity].

The data presented demonstrate possible personal radiosensitivity prognosis according to the immobilization stress response (animal model). It was demonstrated on the Wistar rats that in radiosensitive animals initial oxidative metabolism parameters were higher than in radioresistant ones, and prooxidant-antioxidant balance alteration after non-radiation stress were more evident and kept for a longer period. Those animals had had limphopenia and neutrophilosis. The differences in the response types between radiosensitive and radioresistant animals were due to the blood system reserve abilities, as well as the state of natural mature cells depot, and antioxidant defence enzymes.

Early experimental studies on hemoperfusion as a treatment modality for acute radiation disease.

First results of the studies on hemoperfusion therapy of acute radiation disease that were conducted in Kiev in 1976 are presented. In these studies, 69 mongrel dogs were exposed to irradiation at a dose of 525 rad (5.25 Gy). It was proved that hemoperfusion through uncoated synthetic activated carbons led to a noticeable increase in their survival rate, from 3.2% in the control group (n = 31) to 68.4% and 62.4% for the dogs that received extracorporeal treatment at 2 h (n = 19) and 24 h (n = 19) after irradiation, respectively.

[The biological effects in animals related to the accident at the Chernobyl Atomic Electric Power Station. 2. The state of bone marrow hematopoiesis in rats]. / Biologicheskie éffekty u zhivotnykh v sviazi s avariei na Chernobyl'skoi AES. Soobshchenie 2. Sostoianie kostnomozgovogo krovetvoreniia u krys.

It has been shown that rats born during the first months after the Chernobyl A.P.S. disaster exhibit essential changes in the peripheral blood and bone marrow haemopoiesis throughout the entire lifetime. Rats brought up in Chernobyl from the age of three months on display even more pronounced changes. It is assumed that the changes in the haemopoiesis develop due to the continuous influence of low-level radiation of different quality and are attributed to the effect of the incorporated radionuclides.

[The biological effects in animals in relation to the accident at the Chernobyl Atomic Electric Power Station. 5. Longevity and the carcinogenic effects]. / Biologicheskie éffekty u zhivotnykh v sviazi s avariei na Chernobyl'skoi AES. Soobshchenie 5. Prodolzhitel'nost' zhizni i kantserogennye éffekty.

Remote effects in laboratory animals living in conditions of exposure to a mixture of external and internal radiation resulted from the Chernobyl A.P.S. disaster have been investigated. It has been found that the rate of deaths from non-tumor illnesses grows, the incidence of neoplasms increases and their latency time decreases. The redistribution within the spectrum of benign and malignant tumors and the increase in the multiplicity coefficient have been revealed. It is concluded that chronic exposure of animals to low-level radiation from the radionuclides, resulted from the accident, brings about a much larger number of negative stochastic and nonstochastic remote effects as compared to those expected from the extrapolation of the effects produced by high radiation doses.