ABSTRACT
Difluoromethylornithine (DFMO) was studied for its effect on the aminoxidase activity in the culture media during proliferation and differentiation of mouse fibroblasts. Single introduction of difluoromethylornithine into the culture medium increases the polyamine oxidase activity during 12 to 24 hours after the action. In the subsequent periods DFMO in 0.1 to 1 mM concentrations inhibits the proliferation and differentiation, but 0.01 mM concentration leads to their acceleration, which correlates with higher or lower aminoxidase activities respectively in the culture media.
Subject(s)
Cell Differentiation , Cell Division , Polyamines/metabolism , Animals , Cell Differentiation/drug effects , Cell Division/drug effects , Eflornithine/pharmacology , Fibroblasts/cytology , Fibroblasts/enzymology , L Cells , Mice , Mice, Inbred C3H , Monoamine Oxidase , Monoamine Oxidase Inhibitors , Ornithine Decarboxylase Inhibitors , Oxidation-ReductionABSTRACT
The inhibitory effect of difluoromethylornithine (DFMO) synthesized by the authors on the activity of the ornithine decarboxylase (ODC) and proliferation of microbial and mammalian cells in vitro was studied. The in vivo growth of ascite plasmocytoma of solid melanoma B-16 cells in mice was also effectively inhibited by DFMO. But the antiproliferative activity of DFMO in solid tumours was substantially lower. Such a decrease in the antitumour activity may be associated with polyamines released from necrotic areas of solid tumours. As the tumour cells "catch" the vitally important metabolites, their effect inside solid tumours is turned against the tumour cells themselves. The second reason of the decrease in the DFMO activity is adsorption of polyamines on the erythrocyte surface.
Subject(s)
Antineoplastic Agents/pharmacology , Ornithine Decarboxylase Inhibitors , Ornithine/analogs & derivatives , Animals , Antineoplastic Agents/therapeutic use , Bacillus megaterium/drug effects , Cell Division/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Eflornithine , Escherichia coli/drug effects , Liver Regeneration/drug effects , Melanoma/drug therapy , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Ornithine/pharmacology , Ornithine/therapeutic use , Plasmacytoma/drug therapy , RatsABSTRACT
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 OxidaseSubject(s)
Mycobacterium tuberculosis/drug effects , Tuberculosis, Pulmonary/microbiology , Animals , Antitubercular Agents/administration & dosage , Drug Therapy, Combination , Filtration , Guinea Pigs , Male , Mycobacterium tuberculosis/isolation & purification , Time Factors , Tuberculosis, Pulmonary/drug therapySubject(s)
Antibody-Producing Cells/drug effects , Immunosuppressive Agents , Spermidine/pharmacology , Spleen/drug effects , Animals , Cell Count , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred BALB C , Oxidoreductases Acting on CH-NH Group Donors/blood , Spermidine/administration & dosageABSTRACT
Polyamines excretion with the urine in patients with cancer of the stomach, lung, mammary gland and cervical cancer is considerably increased, as compared with patients having nontumor lesions and healthy individuals. Following a surgical removal of the tumor as well as after chemotherapy the level of polyamines in the diurnal urine is diminished up to normal values. The determination of polyamines excretion may serve as a test for laboratory diagnosis of malignant tumors and also as a criterion of the efficacy of treatment.
