aclarubicin and Sarcoma-180

Two new experimental models of transplantable mouse sarcoma 180 were developed in ICR mice in order to examine the optimum transplantation sites and methods. The cervicodorsal hypoderm was evaluated as the best transplantation site for mouse sarcoma 180 among seemingly usable transplantation sites such as groin, armpit, cervicodorsal, abdominal and lumbodorsal hypoderms by hypodermic transplantation. In addition, the lung transplantation model was established by monitoring the survival period as a reliable parameter for evaluation of anti-tumor effects.

Topics: Aclarubicin; Animals; Antineoplastic Agents; Daunorubicin; Disease Models, Animal; Doxorubicin; Lung Neoplasms; Male; Mice; Mice, Inbred ICR; Neoplasm Transplantation; Sarcoma 180; Skin Neoplasms; Specific Pathogen-Free Organisms

A new anthracycline antitumor antibiotic, aclacinomycin A, was labeled with 3H uniformly or with 14C simultaneously at the anthracycline nucleus and L-rhodosamine. These labeled drugs were administered intravenously to normal dd mice, solid type Sarcoma 180 tumor-bearing ICR mice, normal or pregnant Wistar rats and normal rabbits, respectively. 14C-Aclacinomycin A given to rabbits (5 mg/kg) was rapidly cleared from the blood and transferred to tissues. But low level of radioactivity (equivalent to about 0.5 mcg/ml) was remained in the blood even 8 approximately 10 hours after administration. About 45% of the radioactivity were recovered from the urine and 20% from the feces by 72 hours after administration. Tissue levels of 3H-14C-aclacinomycin A given to normal and tumor-bearing mice were highest in the lungs and spleen. Higher distribution was observed also in the liver and kidneys 2 hours after administration. Bioassay revealed that the drug was present in the lungs and spleen in biologically active form and in the liver and kidneys in inactive form, respectively. In the tumor tissue the radioactivity was low but it persisted for 48 hours. Autoradiography with 14C-aclacinomycin A in rats demonstrated that radioactivity due to the drug distributed in the lungs, spleen, kidneys, thymus, intestine, lymph nodes, bone marrow, salivary gland, hypophysis and pineal body but it was rapidly cleared. About 0.2% of radioactivity given to a pregnant rat were transferred to a fetus when 14C-aclacinomycin A was administered intravenously on the 18 approximately 19th day of pregnancy.

Topics: Absorption; Aclarubicin; Animals; Autoradiography; Carbon Radioisotopes; Female; Male; Maternal-Fetal Exchange; Mice; Naphthacenes; Pregnancy; Rabbits; Rats; Sarcoma 180; Tissue Distribution; Tritium

New anthracycline antibiotics have been isolated from the culture of Streptomyces galilaeus MA144-M1. Among 14 anthracycline compounds, aclacinomycin-A showed the strongest activity in inhibiting leukemia L-1210 and had lower toxicity than others. Antitumor activity of aclacinomycin-A against leukemia L-1210 and P-388, solid sarcoma-180, and lymphosarcoma 6C3HED was examined in comparison with adriamycin and daunomycin. Aclacinomycin-A showed the same degree of activity against leukemia L-1210 and P-388, when administered intraperitoneally, as daunomycin and somewhat less than adriamycin. In oral administration, aclacinomycin-A also exhibited a significant activity on leukemia L-1210. The degree of inhibition of the growth of sarcoma-180 and 6C3HED lymphosarcoma transplanted subcutaneously by aclacinomycin-A was almost the same as that of adriamycin and daunomycin, although the optimal dose was about twice more than adriamycin. Acute cardiotoxicity of aclacinomycin-A by a test using hamsters was more than 10 times lower than that of adriamycin.

Topics: Aclarubicin; Animals; Anthraquinones; Antibiotics, Antineoplastic; Cricetinae; Daunorubicin; Doxorubicin; Electrocardiography; Glycosides; Heart; Leukemia L1210; Leukemia, Experimental; Lymphoma, Non-Hodgkin; Male; Mesocricetus; Mice; Mice, Inbred Strains; Sarcoma 180; Sarcoma, Experimental; Streptomyces