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.

Active principle of blastolysin, comprising ca. 40% of the total weight of Lactobacillus bulgaricus cell wall preparation, has been isolated and structurally studied by chemical and spectral methods. The substance a glycopeptide with Mr aa. 10,000, consists of two tetrasaccharide moieties connected by oligopeptide bridges; glycerophosphate, glucose, and galactose moieties are also attached to N-acetylmuramyl residue of the peptidoglucan core. Tetrasaccharide-containing muramylpeptides were shown to be responsible for the antitumour activity.

Experiments were conducted on animals to study intrathecal injection of agents differing in the mechanism of action: variamycin, mitramycin, reumycin, proxyphein, and prospidin. Their acute toxicity in a single intracerebral injection and chronic toxicity in repeated suboccipital injection were studied. The brains of animals who died or were killed were studied pathomorphologically in different periods. Intracerebrally and suboccipitally injected variamycin and mitramycin induced marked toxic reactions, even the death of animals, and cannot be recommended for the neurooncological clinic. The antineoplastic reumycin, proxyphein, and prospidin cause no toxic reactions of the brain and meninges on injection by the above mentioned methods; they are recommended for approbation in the neurooncological clinic for the treatment of patients with malignant tumors of the brain by injection into the system of the cerebrospinal fluid.

IR and electron spectra of an uracil derivative (antitumor antibiotic reumycin) were studied by low temperature spectroscopy. The experimental data corresponded to the quantum chemistry calculations of electron transmission. On the basis of the spectra interpretation the molecular structure of the reumycin isolated molecules was suggested. pKa of reumycin in aqueous medium was determined by UV spectroscopy.

Experiments on inbred and noninbred mice showed thymalin to potentiate the therapeutic effect of cytostatic drugs. Thymalin treatment was followed by inhibition of tumor growth and dissemination, increase in the animal's life span and amelioration of antitumor drug-induced immunodepression.

A soft agar colony assay using diffusion chamber technique in vivo for studying the sensitivity to chemotherapeutic agents of clonogenic tumor cells of primary ovarian carcinoma was used. The highest cytotoxic sensitivity on human clonogenic tumour cells was observed to cyclophosphamide and 5-fluorouracil. The sensitivity of human ovarian carcinoma to chemotherapeutic agents was dependent essentially on the presence of macrophage in cell culture.

Blastolysin is shown to cause degranulation of mast cells, resulting in a reduction of their histamine content and in their release of mediators that activate eosinophilic leukocytes (EL). These accelerate the deamination of the histamine released by mast cells to the extracellular medium. It is possible that blastolysin acts directly on EL granules which are largely responsible for histamine inactivation.

The literature data and the authors' findings on second tumors in patients treated for Hodgkin's disease are analyzed. Most patients who subsequently developed acute leukemia and solid tumors received chemoradiation treatment, while only few of them were exposed to radiation alone. Acute leukemia and solid tumor development is attributed to application of alkylating drugs. Out of 420 patients under study, leukemia was registered in 2 and solid tumors--in 4 cases.

The disodium salt of 2,6-dimethyl-1,4-dihydropyridine-3,5-bis-carbonyl hydroxyacetic acid (I) used in the mg/kg dose decreases the cyclophosphane toxicity in mice and potentiates the cytostatic activity of cyclophosphane, 5-fluorouracil and arabinosyl cytosine against leukemia P388, murine sarcoma 37 and Walker's carcinosarcoma. Administered alone I exhibits no antitumour activity. The potentiation of the antitumour effect of drugs appears independent of the administration schedule. Biochemical evidence indicates that I does not block DNA synthesis in leukemic cells in vitro, but significantly enhances the DNA-blocking effect of cyclophosphane in the same cells in vivo.

Scalp cooling to prevent alopecia was used in 47 patients treated with anthracyclines for various tumors. Good results were obtained though the course included cyclophosphamide which also causes alopecia. Total beneficial (good + satisfactory) effect was recorded in 36 patients (74.4%) who did not need a wig.

Recent data on the mechanism of animal and human tumour cell differentiation induced by different natural and synthetic agents, including antitumour drugs are reviewed. The central role of plasma membranes of the tumour cells and their receptor patterns in the commitment and terminal differentiation of cells is emphasized. Development of a new approach to the cancer therapy based on the combination of tumour cell differentiation induction and cytotoxic effects is discussed.

Diagnostic potentialities of the use of a new radiopharmaceutical 111In-citrin were studied to assess the hemopoietic status on the basis of examination of 47 cancer patients after chemotherapy. Bone marrow function was assessed on the basis of the visual RP distribution in the bone marrow and a study of quantitative indices of the agent accumulation in various anatomical regions. The results of the study showed that a decrease in the agent accumulation in the flat pelvic bones was determined in patients with stable hemocytopenia. Hyperfixation of the agent was undetectable in the long tubular bones. Raised accumulation of the indicator in the metaepiphyses of the long tubular bones was observed in parallel with lowered accumulation of the agent in the flat bones in the group of patients without hemocytopenia nearly in half of the cases. The accumulation of RP in the rest of the cases did not differ from that in the control group. The results obtained showed that 111In-citrin accumulation in the bone marrow of the long tubular bones indicating its functional rearrangement and the normal level of the indicator accumulation in the main zones of bone marrow hemopoiesis in cancer patients could serve as a favorable prognostic sign for the assessment of hemopoiesis in subsequent courses of cytostatic therapy.

The dependence of murine survival on the intervals between periodic hydroxyurea (HU) injections was studied. The single dose of HU comprised 250 mg per kg. Intervals between injections varied from 5 to 19 hours while their number changed from 6 to 9 in different experiments. A resonant increase in the survival was observed under HU administered every 8-9 or 16 1/2 hours.

The effect of transplantation of rat tumours Jensen sarcoma, sarcoma 45, sarcoma M-1, as well as of inoculation of rat normal connective tissue on the processes of biotransformation of antitumour preparations cyclophosphane (CP), thiophosphamide, prospidine and of model compound nitrosomorpholine (NM) was studied. The study was accomplished by means of the Ames test with indicator bacterial strain Salmonella typhimurium TA 1950 in relation to the reactions of the 1st and the 2nd phases of xenobiotics metabolism. It was shown that the presence of tumours leads to inhibition of both metabolic activation processes of the promutagens NM and CP and the conjugation reactions of genetically active metabolites of these compounds with reduced glutathione. Genetic danger is supposed to be increased during application of antitumour preparations, the mutagenic activity of which is due to the activity of their metabolites. It is noted that the most essential effect on biotransformation processes of NM and CP was exhibited by sarcoma M-1, the most important changes of the biotransformation processes of promutagens being observed in the initial period of pathologic process, i.e. on the 3rd day after inoculation. Transplantation of the normal connective tissue of rats had no effect on reactions of both the 1st and the 2nd phase of metabolism of the promutagens studied.

The effect of daunomycin, carminomycin and doxorubicin on the small intestine was studied on mice morphologically and histologically. The toxic action of these antibiotics in maximum tolerance doses was estimated comparatively. It was shown that the anthracycline antibiotics induced hemodynamic disorders, suppression of the crypt epithelium proliferating activity, dystrophic and destructive lesions in the epithelial cells, a decrease in the number of the cells in the crypts and on the villi and development of a large number of pathological mytoses in the small intestine. Recovery of the population count of the small intestine epithelium was associated with an increase in the mytotic activity of the crypts. It was observed by the 7th day after administration of daunomycin or carminomycin, and by the 15th day after administration of doxorubicin. Comparative estimation of the toxic action of the anthracycline antibiotics on the small intestine by such parameters as the percentage of the pathological mytoses and the number of the cells in the crypts and on the villi indicated that the toxic action of doxorubicin was more pronounced as compared to that of carminomycin or daunomycin.