ABSTRACT
The inhibition of polyamine synthesis by DFMO (2.7 x 10(-3) M) resulted in a decrease of proliferation rate of L and OH-1 cells. The patterns of acid-soluble nuclear proteins were studied by the SDS electrophoresis. The content of protein fraction with molecular weight 25 kD was shown to correlate with the rate of proliferation of cell cultures.
Subject(s)
Cell Nucleus/drug effects , Chromatin/drug effects , Lymphoma/pathology , Neoplasm Proteins/drug effects , Polyamines/antagonists & inhibitors , Animals , Cell Division/drug effects , Cell Nucleus/chemistry , Chromatin/chemistry , Eflornithine/pharmacology , Electrophoresis, Polyacrylamide Gel , L Cells , Lymphoma/metabolism , Mice , Molecular Weight , Neoplasm Proteins/analysis , Solubility , Time Factors , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolismABSTRACT
The K-2-9 preparation was determined to change cis-platinum pharmacokinetics, that resulted in its pharmacodynamics alterations. The higher Pt concentrations in the blood of animals which were given the K-2-9 preparation provided selectivity of cytostatic accumulation in the tumour tissue, that was accompanied by more prolonged inhibition of the DNA synthesis. A decrease in the toxicity of cis-platinum is associated with a change in the elimination pathway and acceleration of its removal from the organism.
Subject(s)
Cisplatin/toxicity , Melanoma, Experimental/drug therapy , Animals , Cisplatin/administration & dosage , Cisplatin/pharmacokinetics , Drug Evaluation, Preclinical , Drug Interactions , Drug Therapy, Combination , Melanoma, Experimental/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Neoplasm Transplantation , Time Factors , Tissue Distribution/drug effectsABSTRACT
Difluoromethylornithine (DFMO)-induced polyamide deficiency has been studied for its effect on the electrophoretic mobility of the Ehrlich ascitic cells in G1, S and G2 phases of the mitotic cycle. The DFMO treatment alters the pattern of the electrophoretic mobility distribution of Ehrlich ascite cells. The most profound changes of the electrophoretic mobility pattern are observed in G1-phase and at the S phase beginning. Exogenic polyamines decrease the electrophoretic mobility of cancer cells, which is accompanied by restoration of the initial pattern of the electrophoretic mobility distribution.
Subject(s)
Carcinoma, Ehrlich Tumor/pathology , Cell Movement , Eflornithine/pharmacology , Animals , Electrophoresis , Interphase , Male , Mice , Mitosis , Tumor Cells, CulturedSubject(s)
DNA/blood , Deoxyribonucleoproteins/blood , Leukemia/blood , Adolescent , Adult , Blood Donors , Child , Child, Preschool , Humans , Leukemia, Lymphoid/blood , Leukemia, Myeloid, Acute/blood , Middle AgedABSTRACT
Serum polyamine oxidase was studied for its effect on normal and transformed fibroblasts, Erlich carcinoma, Zaidela hepatoma and experimental Svec leukaemia cells as well as on K-562 human leukaemia cells. It is found that the cell death was induced by dialdehydes generated by polyamine deamination. Autoradiographically it was shown that dialdehydes cross-link the cell plasma membranes. It is suggested that serum polyamine oxidase is one of the factors responsible for the phenomenon of constitutional resistance which provides subsequent realization of the long-term immune defence.
Subject(s)
Leukemia/metabolism , Neoplasms, Experimental/metabolism , Oxidoreductases Acting on CH-NH Group Donors/pharmacology , Aldehydes/pharmacology , Animals , Carcinoma, Ehrlich Tumor/metabolism , Cattle , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Survival/drug effects , Cells, Cultured , Deamination , Fibroblasts/drug effects , Humans , Liver Neoplasms, Experimental/metabolism , Oxidoreductases Acting on CH-NH Group Donors/blood , Polyamines/pharmacology , Spermidine/metabolism , Polyamine OxidaseABSTRACT
Molecular polymorphism and complex-formation ability of ribonucleases, obtained from blood plasma of healthy persons and of patients with acute leukemia as well as from blood plasma of rats with experimental Svec leukemia, were studied using isoelectric focusing, ion exchange chromatography, gel and membrane filtration techniques. Molecular forms of the enzyme were not altered in leukemic patients and animals as compared with normal state but the ability of the enzyme to form complexes with other blood plasma components was markedly decreased in the pathology. Increase in content of polyamines, found in blood of leukemic patients and animals, might be among the reasons responsible for decrease of the enzyme ability to bind with blood plasma proteins.
Subject(s)
Leukemia/blood , Ribonucleases/blood , Acute Disease , Animals , Child , Chromatography, Gel , Chromatography, Ion Exchange , Humans , Isoelectric Focusing , Leukemia, Experimental/blood , Polyamines/blood , Polymorphism, Genetic , Rats , Rats, Inbred StrainsABSTRACT
By methods of analytical electrophoresis nuclear chromatin proteins of normal and leukaemic hemopoietic rat cells were studied. There were revealed 1--2 extra bands in the histones extracted from chromatin of leukaemic cells. These proteins appear to be identical to histones of H10 type. The majority of nonhistone proteins of nuclear chromatin from normal and leukaemic hemopoietic cells show similar electrophoretic characteristics, whereas there were also found components typical for chromatin of only normal or leukaemic hemopoietic cells.
Subject(s)
Chromatin/metabolism , Hematopoietic Stem Cells/metabolism , Leukemia, Experimental/metabolism , Nucleoproteins/analysis , Animals , Cell Nucleus/metabolism , Chromosomal Proteins, Non-Histone/analysis , Electrophoresis, Polyacrylamide Gel , Neoplasm Transplantation , RatsABSTRACT
Purified cell nuclei from the rat liver and hepatoma-27 cells were used to prepare nuclear membranes from which the enzyme-containing extracts of acid-soluble proteins were prepared. The protein extracts were subjected to disc-electrophoresis in 15% polyacrylamide gel using modified Reisfeld's system. It was found that ribonucleases contained in the acid-soluble proteins of the nuclear membranes of normal liver are represented as several components, and differed by their electrophoretic mobility and also by some other physical and chemical properties from crystalline bovine ribonuclease, as well as from nuclear chromatine ribonucleases.