[Results of the implementation of experimental radiobiological studies according to the C.27 program and prospects of further studies].
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Biomedical subjects
Publications and source records attributed to A N Dedenkov.
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The effect of irradiation, metronidazole and iso-metronidazole on survival and number of tumor cells was analysed in vitro in mice that were inoculated with La-hemocytoblastosis--or Ehrlich-ascites-tumor cells after processing. It was shown that metronidazole and iso-metronidazole nearly have the same radiosensitizing activity on these conditions. The effect was dependent on concentration of compounds and cell type. With intraperitoneal application the iso-metronidazole was eliminated from Lewis-lung-carcinoma more slowly than from blood.
Intraarterial selective injection of serum albumin microspheres into the kidney resulted in embolization of the vessels with microspheres of different sizes. In vivo radiometry made it possible to improve the localization of microspheres and their distribution in the animals' bodies at varying time of observation. Pathomorphological investigations showed optimum sizes of microspheres causing prolonged retention of microparticles at the site of injection without considerable morphological changes of body tissues. The method of using microspheres as a radionuclide carrier was shown to hold promise for therapeutic purposes.
The rate of sodium elimination was shown to be inadequate to sodium uptake in rats exposed to prolonged salt loading, the higher the load, the greater the inadequacy. Sodium distribution between vascular and extravascular spaces of the body was also disproportionate in conditions of both excessive and low sodium uptake.
Combination of chronic salt loading with protein-poor diet produces experimental hypertension with natrium consumption near to physiological. The present model is characterized, compared to the existing one, by stage development, moderate arterial blood pressure elevation and absence of "salt toxicosis" and may be thus considered more adequate for experimental investigation of primary arterial hypertension pathophysiology.
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The paper discusses the effect of a cell differentiation-inducing agent--monomethylformamide--on the growth of ascites hepatoma 22A, Ehrlich ascites tumor, thymoma EL-4, leukemia L1210, Lewis lung carcinoma and hemocytoblastosis La. A single injection of the drug into tumor-bearing mice inhibited the growth of the said neoplasms as shown by cell levels in ascites tumors, node size of Lewis lung carcinoma and survival in animals with hemocytoblastosis La. The analysis of the kinetics of inhibition of growth to be transient. For both tumors, the effect of 0.25 g/kg body weight and more showed exponential growth.
The authors presented the results of experiments on 14 random bred dogs in whom fragmentary osteotomy of the maxilla at the level of 7 perpendicular 7 teeth was performed with subsequent investigation of the volumetric blood flow rate in soft and osseous tissues of the osteotomized fragment using labeled albumin microspheres. The animals were divided into 4 groups (the study group and control groups). The volumetric blood flow rate was investigated over time with the monitoring of the CV system 1 (the 2nd group), 6 (the 3rd group) and 24 h (the 4th group) after operation. The total reduction of the blood flow in the tissues of the osteotomized fragment as compared to that of the control group was 54.5% (in the 1st group), 39.3% (in the 2nd group) and 41% (in the 3rd group). The results of the study showed correlation between the blood flow rate reduction in the soft tissue structures and osseous tissue.
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Monoclonal antibodies (MCA) ICO-1 of IgG3 isotype against 1a-like human antigens were labelled with 131I using chloramine T; a radionuclide-bound fraction was isolated by radiochromatography. Basing on the results of assessment of complement-dependent cytotoxicity against lymphocytes from the lymph nodes of BDF1 mice a conclusion was made that MCA immunological reactivity changed slightly after radionuclide tracer administration. In vitro experiments with a panel of normal and malignant cells showed 131I-MCA binding with cells of mouse lymphoid leukemia L1210 and hemocytoblastosis La as well as with spleen and lymph node normal lymphocytes. During in vivo experiments 131I anti-la MCA at a dose of 30 micrograms (specific activity of 32.10(10) Bq/mmol) was administered intravenously to BDF1 mice with transplantable lymphoid leukemia L1210. Radiometry of the organs 24 h after administration of antibodies showed their accumulation in a solid tumor localized on intestinum tenue mesenteriale. The ratio of concentrations of labelled antibodies (in % of the administered amount per 1 g) of tumor/blood was 2.4, that of tumor/liver--4.5. For normal nonimmune 125I-IgG this rate was 0.4 and 0.7, respectively. A high level of MCA in the blood is a factor decreasing MCA diagnostic potentialities. The use of F(a, b)-fragments may considerably decrease the role of this factor. The data obtained suggest a possibility of the use of MCA ICO-1 for in vivo radioimmunoassays of some hematological tumors.
Distribution of 57Co-bleomycetin in organs and tissues of rats with experimental short-term hyperglycemia was studied. Hyperglycemia was induced by intraperitoneal administration of 40 per cent glucose solution in doses of 1 to 10.4 g/kg. The labeled antitumor antibiotic was also administered intraperitoneally (0.2-0.8 MBq per animal). The data on both the external radiometry in the area under the animal limb and the radiometry of separate organs and tissues showed that hyperglycemia markedly altered pharmacokinetics of the labeled antibiotic and retarded its elimination. With respect to the lungs it even increased the drug tropism and accumulation. This information may be useful in radionuclide diagnosis and therapy in particular of lung cancer. The time course of glucose concentration in blood was not an adequate criterion of hyperglycemia influence since the influence of hyperglycemia on retarding the drug elimination was also observed when the level of glucose in blood did not differ from the initial one.
Experimental studies on rats with sarcoma 45 showed that antitumor efficacy of bleomycetin could be markedly increased by inducing short-term hyperglycemia. It was noted that the theoretical value of the additive effect of these factors was lower than the experimental one. This is in favour of the synergistic mechanism of bleomycetin action under conditions of hyperglycemia.
Whole body radiometry was employed to monitor 22Na radionuclide metabolism in Wistar rats of either sex, aged six months and 1.3 years, kept under normal conditions or on a low-protein diet or during chronic salt load over a period of one year. In all the groups studied, the differences in sodium metabolism according to sex and age were determined. Tissue sodium metabolism was statistically significantly slowed (p less than 0.001) in male and female rats on a high-salt diet compared with the control group. Renal sodium excretion was significantly increased in the high-salt diet group. In the low-protein diet group, tissue sodium metabolism was significantly faster than in control animals, and this both in female (p less than 0.01) and male rats (p less than 0.001). Renal sodium excretion was, however, significantly lower in male rats (p less than 0.001) than in control animals.
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Proceeding from an analysis of the literature and their own data on radio- and thermodifying properties of hyperglycemia the authors have proposed a scheme of polyfactor therapy of malignant tumors including the following succession of exposures under clinical conditions: irradiation (the 1st fraction)--a chemotherapeutic drug--hyperglycemia--hyperthermia--irradiation (the 2nd fraction). The interval between exposures should be the least, best of all exposures should follow one another in a quick succession. Using the experimental data for determination of methods of therapy of transition and metastatic tumors of the upper respiratory tracts, satisfactory clinical results were obtained with regard to survival and the absence of local radiation reactions.
The paper is concerned with the results of a study of the relation of a metastatic spreading of mouse Lewis carcinoma to temperature distribution in the area of a tumor and healthy tissue damage. It was shown that a significant metastatic spreading inhibition was observed in selective MWF-hyperthermia (43-46 degrees C, 30 min). In the absence of a selective hyperthermal exposure when both tumors and healthy tissues were damaged (at the same thermal dose), there was a tendency to metastatic spreading enhancement. A considerable metastatic growth was noted after tumor-affected limb amputation without hyperthermal exposure.
The ability of serotonin, melatonin and beta-endorphin synthesis by secreting granules of natural killer cells (NK cells) was established by immunohistochemical method. It was shown that cytotoxic effect of NK cells can be to a certain extent related to the presence of secreting granules. A possible direct contribution of NK cell-synthesized hormones to the natural killer antitumour effect is discussed.
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