Studies on such transplantable murine tumors as MOPC-21 plasmacytoma and Krebs-2 carcinoma showed oxoplatinum course administration to produce necrosis in solid tumors and pronounced alterations in surviving tumor cells. Single applications of 15 or 20 mg/kg were followed by an increase in the mean survival of Krebs-2 ascites carcinoma--bearing mice by one half. Oxoplatinum--induced changes in the renal tissue ranged from moderate under continuous administration to acute renal failure after high--dose treatment. Such diuretics as diacarb, furosemide and, particularly, mannitol did not interfere with oxoplatinum activity against solid and ascites tumors but assured less pronounced structural disorders in the kidney as compared to oxoplatinum alone.

The hematotoxicity of cytostatics was found enhanced if these agents were used in therapy of oncologic patients with disordered functional activity of the hepatorenal system. Decreased absorption and excretory functions of the hepatocytes or renal abnormalities associated with impaired glomerular filtration and secretory-excretory function are the factors that contribute to the development of leukopenia by the middle or end of the treatment course. This permits a conclusion on the prognostic value of examinations of liver and kidney function in cases with the development of secondary hemodepression in chemotherapy of oncologic patients.

A natural DNA-intercalator plant benzo-c-phenanthridine alkaloid sanguinarine is more toxic for mouse transformed fibroblast L-cells in culture than synthetic DNA-intercalator ethidium bromide (EtB) and alkaloid berberine. Dimidium bromide is also an inhibitor of the L-cell growth. In assay conditions, growth of L-cells is stopped by 1.5 x 10(-5) M of sanguinarine. Lebr-625 cells, resistant to 25 micrograms/ml of EtB, have sanguinarine sensitivity close to that of L-cells, but Lebr-625 cells are resistant to dimidium bromide. Sanguinarine is more toxic for L-cells in culture than the anticancer drug cis-PtNH3)2Cl2. Trans-Pt(NH3)2Cl2 is less toxic for these cells. The strong toxicity of sanguinarine for L- and Lebr-625 cells in culture, as compared to other DNA-complexing drugs, seems to be associated with the wide range of potential cell targets for sanguinarine influence. Besides the inhibition of nucleic acid metabolism reactions, characteristic of DNA-intercalators, and disruption the mitochondrial ATP synthesis, also characteristic of organic heterocyclic cationic molecules of DNA-intercalators, sanguinarine can modify the thiol groups of enzymes including SH-sensitive membrane-bound Na+, K(+)-ATPase of cerebral cortex and Ca2(+)-ATPase of skeletal muscle sarcoplasmic reticulum fragments.

Condensation of daunorubicin or its (13 R, S)-dihydro derivative with inosine dialdehyde in the presence of NaBH3CN yielded novel derivatives of anthracycline antibiotics with incorporated inosine residue: 3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)-hydroxymethylmorpholino-N4"]- daunorubicin and (13 R,S)-dihydro-3'-deamino-3'-[(2" R)-(hypoxanthyl-9)-(6" S)- hydroxymethylmorpholino-N4"]-daunorubicin. The compounds did not inhibit growth of Bacillus mycoides and were less cytotoxic in vitro and less toxic in vivo than the parent antibiotics.

The antiviral activity of anthracycline antibiotics of rhodomycin group was investigated by two independent methods which determined the infectious units or antigenicity of the viruses. The action of rhodomycin depended on the structure, number, and position of amino sugar in aglycon. The antiviral activity was found to increase in serial order: iremycin--adriamycin--daunomycin--alpha-rubicin--beta-rhodom ycin-- violamycin B I complex by inhibition kinetics determined with adenovirus.

The effect of exposition with pretreatment for thiophosphamide and dipin of human lymphocytes at Go phase was investigated. There were used 5 low concentrations of mutagens: 2, 0, 2; 2.10(-2); 2.10(-3), 2.10(-4) mcg/ml with different exposure: 1/4 hr, 1/2 hr, 1 hr and 4 hr and high concentration of 20 mcg/ml by which cell have been treated. There was discovered the dependence of the "protective" concentration on the exposition: the increase of exposition of pretreatment induced the decrease of "protective" concentration and vice versa.

Platidiam, cyclophosphamide and adriamycin induced tumoricidal activity of peritoneal macrophages from patients with disseminated ovarian carcinoma when applied in the autologous tumor cells in vitro. This effect was not observed with 10 micrograms/ml concentration of 5-fluorouracil. The mice peritoneal macrophages after incubation in vitro with 0.01-1.0 micrograms/ml of aclarubicin showed cytostatic action on syngeneic and semisyngeneic P388 cells. The peritoneal macrophages from mice treated with 2.5 mu/kg of aclarubicin intraperitoneally 1-4 days before were cytotoxic for tumor cells too.

The investigation of biological activity of two coordination platinum (II) compounds covalently linked with Fab-fragments of nonspecific immunoglobulin donors on mononuclears of peripheral man blood in vitro and blood elements of mice BALB/c has been done in this paper. There have been stated the decrease of cytotoxic activity of platinum reagents after complexing and modulating influence of platinum-globulin complexes on immunocompetent cells. The prospects of increasing biological activity of immunological preparations on the basis of directed modification by platinum reagents has been also discussed.

It was shown that during glutamate+malate oxidation in the presence of creatine, antitumour anthracycline antibiotics strongly inhibit the rate of oxygen uptake by rat heart mitochondria; ADP excess activated the respiration up to the initial level, i.e., that observed after the first addition of ADP. Carboxyatractyloside addition to a system containing creatine (or hexokinase+glucose) results in the stimulation of rubomycin-induced mitochondrial respiration. Substitution of carboxyatractyloside by oligomycin gives very similar results. It is supposed that anthracycline antibiotics exert a manyfold effect on heart mitochondrial membranes which results in impaired compartmentation of enzymatic systems providing for oxidative phosphorylation.

The effect of anthracycline antibiotics such as carminomycin, daunomycin (rubomycin) and adriamycin on respiration and synthesis of nucleic acids and protein was studied comparatively. The anthracyclines inhibited the processes. By their efficacy in that respect they could be arranged in the following order: carminomycin greater than rubomycin greater than adriamycin. Thus, 50 per cent inhibition of nucleic acid synthesis in the thymocytes required 0.027, 0.044 and 0,173 mM of carminomycin, rubomycin and adriamycin respectively. Protein synthesis and respiration in the thymocytes were less sensitive to the effect of the anthracyclines than synthesis of nucleic acids. The study results were compared with the literature data on the effect of the compounds on respiration and synthesis of nucleic acids and protein in tumour and bacterial cells.

On the 5th day after intraperitoneal injection of cisplatin the rats developed renal insufficiency. The concentration of creatinine and urea in blood serum increased 9-fold, the glomerular filtration rate decreased 7.7-fold, the weight of kidney increased by 44%. The content of tissue sodium was found to increase, while that of K to decrease. The intraperitoneal injections of cycloplatam (up to 25 mg/kg) induced in rats no renal insufficiency, the kidney weight and the ion and water content in the tissue did not change. In the experiments with cisplatin the Pt level in kidney reached 59.1 +/- 3.05 micrograms/g dry substance, after the injection of cycloplatam 25 mg/kg it was 104.9 +/- 2.95. No nephrotoxic action of cycloplatam may be due to the presence in the molecule of the cyclopentyl substitute.

Studies were carried out of changes in lipids composition, their antioxidative activity (AOA) and oxidizability, as well as of the viscosity of different regions of the liver cells nuclear membrane after single injection of diasan (1,2-bis-diasoacetyletan) (class of diasoketones) possessing antitumor activity in the experiment. On the basis of the results obtained the state of membrane control system was analysed. In vivo injection of diasan was found to bring about changes in AOA--membrane viscosity interaction in the system as compared to the norm. These changes are due to distortion of AOA--lipids composition--oxidizability interaction at earlier times, and of lipids composition--membrane viscosity interaction at later times. The experimental data are discussed in terms of a theoretical model of functioning of this control system in response to stimulation. A number of hypotheses are advanced concerning the role of some interactions of the system for the cell metabolism in the norm and antitumor effect of diasan from the standpoint of the control system under consideration.

It was shown in experiments on anesthetized rats that intramuscular administration of dipidolor (5 mg/kg) failed to exert any effect on the functioning of the cardiovascular and respiratory systems of the animals which previously had been irradiated with the dose of 50 Gy or given intravenous injections of platidyam (5 mg/kg) or cyclophosphane (50 mg/kg).

Natural human leukocyte interferon (50 IU/ml), added to human lymphocytes for 24 hour incubation time, increased the background sister chromatid exchange (SCE) frequency and shortened the average generation time (AGT). Interferon pretreatment decreased the levels of the SCE induced by antineoplastic alkylating drug fopurin (2-dimethylamino-6-diethylene iminophosphamido-7-methylpurine; treatment conditions: the 20-24 hour incubation time, 25 and 50 microM), but no statistically significant changes were noticed in AGTs, in the number of aberrant metaphases, and in the total number of induced chromosome aberrations (CA). The increased number of the exchange-type CA induced by fopurin (50 microM) was observed in interferon pretreated cells. The results obtained indicate different formation mechanisms for SCE and CA, as well as different modification ways of SCE and CA formation by interferon.

The effect of 21 methionine-platinum(II) and (IV) complexes on growth and division of cells in maize seedling roots has been studied. The studied complexes did not possess properties inherent in typical cytostatic compounds, e.g. cis-dichlorodiammineplatinum (DDP). They inhibited root growth at higher concentrations as compared to DDP. In contrast to DDP, the studied complexes inhibited cell elongation to a similar or greater extent than cell division, did not prevent lateral root formation, and their inhibitory effect did not change with time. No correlation between the level of tumor growth inhibition and the pattern of root growth was observed.

Antitumour antibiotic from a plant of the family Asteracea has been studied for the biochemical mechanism of its action. Redox processes were tested by the method of spontaneous chemiluminescence determining the intensity of freely radical oxidation of membrane cell phospholipids. It was established that the antibiotic under study stabilized the indices of spontaneous chemiluminescence up to the normal level.