melphalan and Sarcoma-37

The two DNA fractions were isolated from sarcoma 37 by the use of the phenol method: supramolecular complex of DNA (SC DNA, 60%) and "phenol" nuclear matrix DNA (PNM DNA, 40%). The lipids in SC DNA represented of light and tightly bound components, the latter was similar to the lipid composition of PNM DNA. SC DNA contains 20 micrograms of neutral lipids (NL) and 6.5 micrograms of phospholipids (PL), while PNM DNA contains 9.8 micrograms of NL and 3.5 micrograms of PL per mg DNA. SC DNA-bound lipids of sarcoma 37 are deficient in free cholesterol (FC, 13%), but rich in cholesterol esters (CE, 39%) and free fatty acids (FFA, 23%); very rich in cardiolipin (CL, 43%) and phosphatidylethanolamine (PE, 28%), but deficient in phosphatidylcholine (PC, 12%). The tumor contains triglycerides (TG) that is absent in DNA of the normal cells. The injection of sarcolysine (10 micrograms/kg) markedly increased (1.5-3 times) the content of all LN and PL fractions in SC DNA, which was accompanied by both the accumulation of FC, TG, PC and the reduction of the remaining lipid fractions in PNM DNA. It is supposed, that DNA-bound lipids may be the target for the action of sarcolysine.

Topics: Animals; Chromatography, Thin Layer; DNA, Neoplasm; Drug Evaluation, Preclinical; Lipids; Male; Melphalan; Mice; Sarcoma 37; Sarcoma, Experimental

Sarcolysine-induced damaging and reparative processes in the primary structure of tumour cell DNA have been studied. The presence of low sarcolysine concentrations (1 mkM) in the cell culture during the first two hours of incubation caused suturing of DNA molecules. The increase of the incubation time from 4 to 18 hours and the rise in the drug concentration (by 10.20 times and more) resulted in intensive accumulation of one-strand breaks. However, we have not observed the appearance of high-molecular DNA, which is the evidence of the completion of the reparative process. The impulse treatment with sarcolysine (1 hour, 10 mkM) with subsequent drug removal caused the irreversible damage of DNA reparative processes at the stage of short fragments' suturing.

Topics: Animals; DNA Repair; DNA, Neoplasm; DNA, Single-Stranded; Dose-Response Relationship, Drug; In Vitro Techniques; Male; Melphalan; Mice; Sarcoma 37; Sarcoma, Experimental; Time Factors

The sites of specific binding of 3H-L-dihydroalprenolol (3H-DHA) were identified on the surface of ascites sarcoma 37 cells, using competitive displacement and binding of the beta-adrenergic antagonists, 3H-DHA and L-propranolol. These binding sites possessed the properties of beta-adrenergic receptors coupled with adenylate cyclase. Analysis of 3H-DHA binding by the Scatchard method revealed the presence of beta-adrenergic receptors of two types, i. e., with a high (Kd = 0.9-1.0 nM) and low (Kd = 15-20 nM) affinity for 3H-DHA. The number of high affinity receptors was (5.0-7.5) X 10(3); that of low affinity receptors was (20-30) X 10(3) on a per cell basis. Sarcolysine at concentrations of 1-10 microM displaced receptor-bound 3H-DHA, competed with the ligand for the common binding sites and caused, similar to isoproterenol, a short-term elevation of the intracellular cAMP content. Sarcolysine within the same concentration range (2.5-25 microM) caused non-competitive inhibition of the cAMP phosphodiesterase (PDE2) activity of plasma membranes isolated from ascites sarcoma 37 cells. The data obtained point to the functional coupling between beta-adrenergic receptors, adenylate cyclase and membraneous PDE2 of tumour cells as well as to its possible role in the antitumour effect of sarcolysine.

Topics: Adenylyl Cyclases; Animals; Binding Sites; Binding, Competitive; Dihydroalprenolol; In Vitro Techniques; Kinetics; Melphalan; Mice; Models, Biological; Propranolol; Receptors, Adrenergic, beta; Sarcoma 37; Sarcoma, Experimental

Topics: Adenocarcinoma; Amino Acids; Animals; Antineoplastic Agents; Copper; Drug Therapy, Combination; Female; Intestinal Neoplasms; Lung Neoplasms; Mammary Neoplasms, Experimental; Melphalan; Mice; Neoplasms, Experimental; Rumen; Sarcoma 37; Uterine Cervical Neoplasms

The use of spectrophotometric method of objective quantitative estimation of tumor cells growth in diffusion chambers and chemotherapeutic sarcolysin effect on them are described.

Topics: Animals; Culture Techniques; Melphalan; Mice; Nucleic Acids; Sarcoma 37; Spectrophotometry, Ultraviolet

Topics: Animals; Antineoplastic Agents; Carcinoma 256, Walker; Carcinoma, Ehrlich Tumor; Female; Leukemia, Experimental; Leukocyte Count; Lymphoid Tissue; Male; Mammary Neoplasms, Experimental; Melphalan; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Neoplasms, Experimental; Organ Size; Ovarian Neoplasms; Rats; Sarcoma 180; Sarcoma 37; Sarcoma, Experimental; Spleen; Splenic Neoplasms; Thymus Gland; Thymus Neoplasms; Time Factors; Triazines

Topics: Animals; Antineoplastic Agents; Melanoma; Melphalan; Mice; Sarcoma 37; Sarcoma, Experimental

Topics: Animals; Carcinoma, Ehrlich Tumor; Male; Melphalan; Mice; Neoplasms, Experimental; Polymers; Sarcoma 180; Sarcoma 37

Topics: Animals; beta-Aminoethyl Isothiourea; Cyclophosphamide; Cystamine; Melphalan; Mice; Nitrogen Mustard Compounds; Rats; Sarcoma 37; Sarcoma, Experimental; Uracil

Topics: Adenocarcinoma; Animals; Fluorides; Injections, Intraperitoneal; Leukemia, Experimental; Leukemia, Lymphoid; Mammary Neoplasms, Experimental; Melphalan; Mice; Phenformin; Sarcoma 37

Topics: Animals; beta-Aminoethyl Isothiourea; Bone Marrow; Bone Marrow Cells; Depression, Chemical; Leukocyte Count; Male; Melphalan; Mice; Neoplasm Transplantation; Sarcoma 37; Streptomycin