The cardiotoxic effect of karminomycin and adriamycin administered intravenously for 5 times in equitoxic doses constituting equal portions of LD50 of the respective antibiotic on its single intravenous administration was studied on albino mice. Histological examination of the heart showed that almost identical damages of the myocardium occured after administration of karminomycin and adriamycin in doses of 0.45 of LD50 (1.5 mg/kg) and 0.3 of LD50 (6.3 mg/kg) respectively. The character of the damages due to the antibiotics was close, the most significant changes were observed when the animals were sacrificed 1 month after the last administration of the drug. The histological method is of value in estimation of the cardiotoxic effect of the drugs, using mice as the model suitable for the investigation. Adriamycin had more pronounced cumulative properties as compared to karminomycin: suppression of the weight gain in the mice and their death rate were higher with the use of adriamycin.

LD50 of karminomycin, rubomycin and adriamycin were determined after their single administration or 3-, 5-, 10- and 15-fold administration once a day to 540 hybrid male mice F1(C57B1 X CBA). Comparison of the cumulative indices for these antibiotics showed that after injections they were close. After 5 injections the cumulative properties were more pronounced for adriamycin. After 10 or 15 injections the cumulative properties were less pronounced for karminomycin.

The variants of the tumor cells of Fisher lymphadenosis, strain L-5178 and Staph. aureus resistant to rubomycin simultaneously became partially less sensitive to adriamycin. Sensitivity to karminomycin in the rubomycin resistant strains did not practically change as compared to the sensitivity of the initial strains. Sensitivity to adriamycin and rubomycin in Staph. aureus decreased 67 and 4 times respectively after 7 passages on media with increasing concentrations of adriamycin, while sensitivity to karminomycin decreased only 1.5 times, i.e. remained practically unchanged. After 22 passages of Staph. aureus to karminomycinrubomycin and adriamycin decreased 16, 67 and 33 times respectively. The results of the study may be explained by differences in the changes of the cell membrane permeability due to the drug effect.

Karminomycin was more toxic with respect to 2-6 week mice than to adult animals when administered both intravenously or orally. 5-6 week rats were more stable than adult animals to the effect of karminomycin administered intravenously or orally. Significant species sensitivity to karminomycin was noted. When administered intravenously karminomycin administered intravenously was 2 times more toxic as compared to the oral use in the experiments with adult mice and 23 times more toxic in the experiments with adult rats. LD10 and LD50 of rubomycin administerean in adult animals. LD50 of karminomycin and rubomycin administered intravenously to adult female mice was somewhat lower than that for adult male mice.

Anthracycline antibiotics, such as rubomycin C (rubomycin, daunomycin), rubomycin B, carminomycin and tavromycetin (cinerubin) significantly increased the bactericidal effect of ultraviolet radiation and mitomycin C with respect to mutant 19-8 of E. coli with increased permeability of the cell membrane. This may be accounted for inhibition of DNA reparation. Beromycin, an antibiotic of the same group had no such capacity. With respect to their activity the antibiotics were arranged as follows: rubomycin C, rubomycin B, carminomycin, tavromycetin.

The mutants of Saccharomyces cerevisiae, strain FL 599-I B with defect cell membranes are selectively inhibited by anticancer antibiotics with different molecular mechanisms of action on DNA. At the same time they are insensitive to antibacterial antibiotics. Such mutants may be used as test-cultures in isolation of active agents with antitumor effect from complex mixtures of natural substances. The above test-object makes it easier to perform separation of antimour antibiotics from accompanying bacterial inhibitors.

Tests staged with mice and rats demonstrated 5-fluorouracil, fluorafur, methotrexate, cyclophosphane and vinblastine capable of inhibiting to a different degree the primary immune response and the factors of nonspecific immunity. Methotrexate displays the highest activity and specificity of the immunodepressive effect. By using different doses of the drug in immunizing the animals with sheep erythrocytes and vi-antigens the factors of both specific and non-specific immunity were inhibited in all cases. With their single introduction 5-fluorouracil and fluorofur can stimulate the synthesis of humoral antibodies and have no effect on the immune response. With their multiple administration the immunological reactivity of the organism becomes depressed. The extent of changes involving non-specific factors doses not depend upon the pattern and schedule of the drug administration. Cyclophosphane and vinblastin inhibit the immune response when they are introduced 24 hours after immunization. Vinblastin had the faculty of bringing down the activity of the nonspecific immunity, whereas under the effect of cyclophosphane it did not change, except for the complement.

Systems of blood coagulation in patients treated with antibiotics of the anthracycline group were studied. Rubomycin was used in the treatment of patients with acute leukemia Adriamycin and carminomycin were used in the treatment of patients with solid tumors. The antibiotics affected the process of blood coagulation mainly through their cytostatic effect on thrombocytopoesis. Thrombocytopenia induced deficit of thrombocytal factors participating in the process of blood coagulation which resulted in hypocoagulation and hemorrhagic complications. The plasmic factors did not significantly change during the antibiotic therapy. A tendency to decrease in the levels of prothrombine, fibrinase and fibrinogen was noted which was possible due to an inhibitory effect of the antibiotics on the function of the reticuloendothelial tissue cells or indirectly to suppression of the tumor process. More pronounced changes in the system of blood coagulation of patients treated with rubomycin were probably associated with inferiority of the thrombocytal apparatus of the patients with acute leukemia treated with the antibiotic.

The parameters of the lethal effect of aureolic acid derivatives, such as mithramycin, variamycin and olivomycin were studied on mice, rats and rabbits. As for the most of the administration routes the first two drugs were characterized by irregular distribution of resistance to thier lethal effect, which was mathematically expressed by polymodality of the dose-response curve. The above drugs were characterized by cumulative properties. The toxicity parameters depended on the animal species and administration route.

The side effect of reumycin, an antitumor antibiotic was studied experimentally. The average lethal dose for mice and rats on intravenous administration of the drug was 45.5 and 42.2 mg/kg respectively. When reumycin was administered to rats and dogs for prolong periods of time, an increase in the levels of total protein, urea nitrogen and inorganic phosphorus in the blood was observed, while the levels of hemoglobin and thrombocyte counts decreased, the process of the blood coagulation being slower. The changes in the ECG were similar to those observed in the myocardium dystrophy. The morphological changes in the organs were characterized by perivascular edema, swelling of the vessel walls and edema of the interstitial tissues.

A substrain of the ascitic leucosis P-388 was obtained as a result of interchanging passages of P-388 leucosis cells in the primary cultures and abdominal cavity of mice. The tumor cells of the ascitic leucosis P-388 multiplied in the primary suspended culutres as well as in vivo. The substrain lost its hemorrhagic properties. The content of DNA and RNA in the primary cultures of P-388 doubled every 16-18 hours and the number of the cells doubled every 24-26 hours. The cells of the adapted substrain of P-388 grew also in the semiliquid agarized medium forming compact colonies by the 4th-5th day of cultivation. The primary suspended cultures of P-388 were highly sensitive to cytostatics and in particular to vinblastin and kolchamine (alkaloids). In this connection they were recommended for prescreening antitumor compounds.

Utilization of endolymphatic infusions against the background of the impaired barrier function of lymph nodes is inherent in a higher rate of tumor metastasization. The hazard increases in cases when tumore cells in the lymph system (especially in the thoracic duct) are in a free state, and substances dilating lymph vessels are employed. Therefore, endolymphatic infusions should be accomplished taking into account all the factors that could lower either directly or indirectly the barrier function of the lymphatic system.