carubicin and Carcinoma--Ehrlich-Tumor

Antitumor activity of doxorubicin made in the USSR was studied on mice in respect to three transplantable tumors (lymphadenosis NK/LI, sarcoma 37 and Ehrlich's carcinoma) and hemocytoblastosis La. Doxorubicin injected intravenously 4 times was shown to be highly active against the above ascites tumors. The highest inhibitory effect of doxorubicin was observed in respect to the development of Ehrlich's carcinoma. By the selectivity of the therapeutic effect on this tumor it was superior to rubomycin and carminomycin. A high antileukemic activity of doxorubicin in respect to hemocytoblastosis La was shown. In experiments with this leukemia, intravenous injection of doxorubicin provided a higher efficacy than intraperitoneal injection. When used intravenously in the doses equivalent by their toxicity doxorubicin was inferior to rubomycin in terms of the therapeutic effect on leukemia La. However, on intraperitoneal injection of the drugs rubomycin showed no such advantage. Doxorubicin made in the USSR did not differ by its antitumor activity from the analogous foreign drug.

Topics: Animals; Carcinoma, Ehrlich Tumor; Carubicin; Daunorubicin; Dose-Response Relationship, Drug; Doxorubicin; Injections, Intraperitoneal; Injections, Intravenous; Leukemia, Experimental; Lymphoma; Male; Mice; Mice, Inbred C57BL; Sarcoma, Experimental

It was found with the method of sedimentation analysis in sucrose alkaline gradients that carminomycin induced in vivo degradation of the DNA-membrane complex of the Ehrlich's ascites carcinoma cells (EAC). The concentration dependence of the complex damage correlated well with the data on the cell survival: the subtoxic concentration of the antibiotic according to these tests was 0.001 micrograms/ml. Combined effect of carminomycin in the subtoxic concentration and gamma-radiation on the cells did not result in any increase in the primary radiation damage to the DNA-membrane complex. Still, it inhibited its post-radiation reparation. This suggested that on the combined use of the above damaging agents the antibiotic significantly increased the effect of the ionizing radiation on the cells.

Topics: Animals; Carcinoma, Ehrlich Tumor; Carubicin; Cell Membrane; Cells, Cultured; Daunorubicin; DNA Repair; DNA, Neoplasm; Gamma Rays; Mice; Neoplasm Transplantation

The kinetics of cellular and nuclear incorporation of a number of new anthracyclines into daunorubicin-sensitive and -resistant Ehrlich ascites cells were determined in vitro. For comparative quantitative analyses the substances were extracted with a 0.3 N HCl/50% ethanol (v/v) solution from either whole cells or purified citric acid nuclei after various intervals of in vitro incubation. At steady state the intracellular and intranuclear concentrations of daunorubicin and doxorubicin were reduced by about 50% in the resistant cell line. Marcellomycin and carminomycin concentrations were only reduced by 9% and 11%, respectively, and no differences between sensitive and resistant cells were seen in the case of aclacinomycin A and AD 32. When the ratios of nuclear to cellular drug were determined at steady state lowest value was found for AD 32 (0.26). In contrast, aclacinomycin A and carminomycin were mainly (78% and 74%) and marcellomycin almost exclusively (95%) concentrated in the nucleus. When the total amounts of drug incorporated per cell were compared, the highest values were measured for aclacinomycin A and the lowest for AD 32 both in the sensitive and the resistant tumor. Additional determinations of the 50% inhibitory concentrations for thymidine uptake showed similar differences between these anthracyclines which were not related to the potency of the drugs in vivo. It is concluded that apart from nuclear incorporation and inhibition of DNA synthesis other factors may be decisive for anthracycline-induced cytotoxicity.

Topics: Aclarubicin; Animals; Anthracyclines; Antibiotics, Antineoplastic; Carcinoma, Ehrlich Tumor; Carubicin; Cell Nucleus; Daunorubicin; DNA, Neoplasm; Doxorubicin; Drug Resistance; Female; In Vitro Techniques; Mice; Naphthacenes

Carminomycin added to the cell culture of Ehrlichs ascites carcinoma (EAC) induced single breaks in DNA whose number increased proportionally to the amount of the antibiotic and the incubation time with it (up to 1 hour). The relationship between the incubation time and DNA injury is first of all defined by the necessity for the antibiotic metabolic activation or the properties of endonucleases. No increase in the number of one-thread breaks during the incubation period of 60 to 120 minutes indicated a possible reparation of DNA injury induced by the antibiotic in the late periods. The exposure of the EAC cells to carminomycin before gamma-irradiation did not result in any increase in the primary radiation injury to DNA but suppressed DNA postradiation reparation.

Topics: Animals; Carcinoma, Ehrlich Tumor; Carubicin; Daunorubicin; DNA Repair; DNA, Neoplasm; DNA, Single-Stranded; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; In Vitro Techniques; Mice; Thymidine; Time Factors

The antiblastomic activity of the carminomycin complex components was studied with respect to 8 strains of transplantable tumors of mice: lymphosarcoma L10-1, prestomach cancer OZh-5, sarcoma 180, lymphoid leucosis L 1210, lung bronchogenic cancer RL, lymphodenosis NK/LI, Ehrlich carcinoma and Garding-Passy melanoma. It was shown that components I, II and III possessed almost the same high antiblastomic activity and the same optimal administration schemes should be used for them. The scheme consisted of two-fold administration of the drug at intervals of 96-120 hours. Component I had broader therapeutic ranges and was more active against the lung bronchogenic cancer as compared to component II. All 3 components had no selective antiblastomic effect on the ascitic form of Ehrlich carcinoma. A comparative study of the component toxicity and pharmacology is required for final conclusion as to the recommendation of one of the components for clinical trials.

Topics: Animals; Antibiotics, Antineoplastic; Carcinoma, Bronchogenic; Carcinoma, Ehrlich Tumor; Carubicin; Drug Evaluation, Preclinical; Lethal Dose 50; Leukemia L1210; Lung Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Melanoma; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Neoplasms, Experimental; Sarcoma 180; Time Factors