vitamin-k-semiquinone-radical and Carcinoma--Ehrlich-Tumor

Ca2+ retention in mitochondria, opening of the Cysclosporin A- sensitive permeability transition pore and cell death were studied in Ehrlich ascites tumour cells in the presence of different prooxidants. Low concentrations (1-20 microM) of the prooxidants (menadione, cumenehydroperoxide, t-butylhydroperoxide) induced pore-opening in permeabilized cells at threshold Ca2+ load. Incubation of cells with low concentrations of prooxidants was able to induce cell cycle disturbance and cell death. Under the prooxidant effect, mitochondrial membrane potential drop and Ca2+ retention decrease in mitochondria were found to precede death of Ehrlich ascites tumour cells.

Topics: Animals; Benzene Derivatives; Calcium; Carcinoma, Ehrlich Tumor; Cell Death; Cell Survival; Intracellular Membranes; Membrane Potentials; Mice; Mitochondria; Oxidants; Oxidative Stress; Permeability; Peroxides; tert-Butylhydroperoxide; Tumor Cells, Cultured; Vitamin K

To study the effect of menadione (Men) reducing doxorubicin (Dox) resistance in Ehrlich ascites carcinoma (EAC) cells resistant to Dox (EAC/Dox cells).. Glutathione (GSH) content and membrane fluidity were measured by fluorometric assay and fluorescence depolarization assay, respectively. Glutathione S-transferase (GST) activity was measured with 1-chloro-2,4-dinitrobenzene as the substrate. Cell viability was determined by 3-(4, 5-dimethylthiazol)-2, 5-diphenyltetrazolium bromide assay.. GSH content, GST activity, and membrane fluidity in EAC/Dox cells were higher than those in EAC cells (P < 0.01). The IC50 (95% confidence limits) for Dox on EAC/Dox cell was 22.3 (15.8-28.8) mg.L-1. Relative resistance of Dox in EAC/Dox cells was 42-fold. Pretreatment of EAC/Dox cells with Men 5 or 10 mg.L-1 decreased intracellular GSH content (P < 0.01). Men 1 mg.L-1 had no obvious effect on GSH content in EAC/Dox cells (P > 0.05), but decreased the elevated membrane fluidity efficiently (P < 0.05). Men had no obvious effect on GST activity in EAC/Dox cells (P > 0.05). IC50 of Dox was reduced to 9.6 (7.8-11.3), 6.0 (2.8-9.2), or 5.3 (3.9-6.7) mg.L-1 in EAC/Dox cells pretreated with Men 1, 5, or 10 mg.L-1.. Men reduced Dox resistance effectively due in part to its depletion of GSH content in EAC/Dox cells.

Topics: Animals; Carcinoma, Ehrlich Tumor; Doxorubicin; Drug Resistance, Neoplasm; Glutathione; Glutathione Transferase; Membrane Fluidity; Tumor Cells, Cultured; Vitamin K

The stress-induced redistribution of cellular proteins between Triton (X-100)-soluble and Triton-insoluble fractions was studied in EL-4 thymoma and Ehrlich carcinoma cells. It was shown by electrophoresis and immunoblotting that a common sign of the cells which in vitro underwent such different harmful influences as ATP depletion, heat shock, oxidative stress, and SH reagent treatment was significant insolubilization of actin and 70-kDa heat-shock protein (hsp70). At the same time, each type of injury caused the specific insolubilization of some major cellular proteins. The transient ATP deprivation alone (without protein denaturation) induced a rapid insolubilization of myosin that was the earliest manifestation of ATP deficiency in the cells. Thermal stress without sharp decrease in ATP level induced a transition of 90-kDa heat-shock protein (hsp90) and 47-kDa polypeptide in Triton-insoluble fraction. The insolubilization of myosin and 47- and 35-kDa proteins was typical for the cells subjected to oxidative stress or SH reagent treatment, both of which caused damage of cellular proteins as well as ATP loss. The redistribution of the above proteins was intrinsic in the stressed cells of either ascites cell line, allowing one to consider it as characteristic and stress-specific cellular response to various injuries.

Topics: Actins; Adenosine Triphosphate; Animals; Carcinoma, Ehrlich Tumor; Heat-Shock Proteins; Hot Temperature; Hydrogen Peroxide; Neoplasm Proteins; Octoxynol; Oxidation-Reduction; Rotenone; Solubility; Thymoma; Tumor Cells, Cultured; Vitamin K

Resting ascites tumour cells (Ehrlich and EL-4 thymoma) treated with menadione (50 microM) died (up to 80% cell death over 2 h) without dividing (i.e. interphase). Glucose (25 mM) added to the cell suspensions partially protected these cells from menadione action. During incubation of the cells with menadione, the rates of free oxidation and lipid peroxidation were elevated, cellular ATP and nonprotein SH-group levels were much decreased, and [Ca2+]i was moderately increased. From a comparison of these effects and cell survival rates with those seen with rotenone, KCN (both inhibitors of oxidative phosphorylation), and H2O2 (an inducer of oxidative stress), it is concluded that ATP depletion is the main factor leading to the death of cells treated with menadione. The level of cellular ATP dropped to less than 10% of its initial value after 1 h incubation with menadione and may have resulted in irreversible damage to cytoskeletal structures, bleb formation, and changes in plasma membrane permeability that are incompatible with cell viability.

Topics: Adenosine Triphosphate; Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Energy Metabolism; Glucose; Glycolysis; Hydrogen Peroxide; Lipid Peroxidation; Mice; Mice, Inbred C57BL; Oxidation-Reduction; Potassium Cyanide; Rotenone; Superoxide Dismutase; Thymoma; Thymus Neoplasms; Tumor Cells, Cultured; Vitamin K

Measurements of the deoxyribonucleoside triphosphate (dNTP) contents, the [14C] thymidine and deoxyuridine incorporation and the "key enzymes" of the thymidine triphosphate (dTTP) synthesis, thymidine kinase and ribonucleotide reductase, in diploid Ehrlich-ascites carcinoma, under the application of hyperthermia, vitamin K and cytocidal agents show: The effect of hyperthermia and menadion (the basic substance of the K vitamins) on the above parameters of dNTP synthesis can explain the labile effects of hyperthemia and vitamin K therapy on cancer growth. Alterations of the dNTP concentrations and demonstrable or absent inhibition of the ribonucleotide reduction with application of fluoruracil, amethopterine, cytosine arabinoside, hydroxyurea, trisethylen iminobenzochinone and daunomycin confirm and supplement our knowledge of the cytostatic action mechanism of these substances. They show moreover by the example of fluoruracil and amethopterine medication that the dTTP concentration estimation after in-vitro incubation of tumour cells with the addition of FU or methotrexat is a better measurement of the therapeutic in-vivo responsiveness of malignant tumours than the previously performed test methods.

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Deoxyribonucleotides; Hyperthermia, Induced; Thymidine Kinase; Thymine Nucleotides; Vitamin K

Topics: 4-Nitroquinoline-1-oxide; Animals; Carcinoma, Ehrlich Tumor; Cell Survival; Cells, Cultured; Cytochromes; Electron Transport; Free Radicals; Glucose; Hydrogen Peroxide; In Vitro Techniques; Microsomes; Nitrofurans; Nitroquinolines; Oxidation-Reduction; Oxygen Consumption; Vitamin K

The action of derivatives of polyoxyethylene oxide (triton X-100, triton X-305, tween 21, tween 40, tween 60, and tween 80) on respiration of Ehrlich's tumor and rats ovarium tumor cells involved inhibition of the cells respiration due to alteration of commonly uncorrelated with the distribution of detergents between the cell and the extracellular milieu.

Topics: Animals; Antimycin A; Carcinoma, Ehrlich Tumor; Cytochromes; Dose-Response Relationship, Drug; Female; Glycolysis; In Vitro Techniques; Neoplasms, Experimental; Ovarian Neoplasms; Oxygen Consumption; Polyethylene Glycols; Polysorbates; Quaternary Ammonium Compounds; Rats; Rotenone; Spectrum Analysis; Tetramethylphenylenediamine; Vitamin K

In a previous paper, the exact conditions under which the radioactive drug 2-methyl-6,7-ditritio-1,4-naphthaquinol bis disodium phosphate could be selectively incorporated into HEp/2 cells were reported. This work has now been extended and suggests that the selective property associated with two human tumour cell lines established in culture, HEp/2 and HeLa, and two forms of mouse ascites tumour cells propagated in vivo, is a metabolic conversion of the drug (priming stage) to a form which can probably be freely incorporated by all cell types. It is suggested that the observed variations in uptake of label with changes in pH, cell concentration and the inorganic phosphate concentration of the medium indicate that the "priming" stage is critically dependent on the conditions of the experiment.Work with the non-radioactive analogue, Synkavit, indicates that under conditions where the drug is incorporated selectively into cells, incubations in excess of 20 minutes cause a large percentage of the population to lose its reproductive integrity.

Topics: Animals; Carcinoma; Carcinoma, Ehrlich Tumor; Cell Division; Cell Line; Culture Techniques; Haplorhini; HeLa Cells; Humans; Hydrogen-Ion Concentration; Kidney; Laryngeal Neoplasms; Male; Mice; Neoplasms; Phosphates; Tritium; Vitamin K

Topics: Animals; Anti-Bacterial Agents; Antimetabolites; Carcinoma, Ehrlich Tumor; Cytochromes; Cytoplasm; Depression, Chemical; Glucose; Glycolysis; Kinetics; Mice; Microsomes; Mitochondria; Oligomycins; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen Consumption; Polarography; Polyploidy; Pyruvates; Rotenone; Solubility; Spectrophotometry; Stimulation, Chemical; Temperature; Time Factors; Uncoupling Agents; Vitamin K

Topics: Adenine Nucleotides; Animals; Argon; Biological Transport; Carcinoma; Carcinoma, Ehrlich Tumor; Cytoplasm; Dicumarol; Electron Transport; Female; Glucose; Glycolysis; HeLa Cells; Hexosephosphates; Humans; Kinetics; Mice; Mitochondria; NAD; Oxidoreductases; Oxygen Consumption; Polarography; Rotenone; Uterine Neoplasms; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Cytoplasm; Depression, Chemical; Dicumarol; Flavins; Fluorescence; Fluorometry; Mice; Mitochondria; Neoplasm Proteins; Oxidative Phosphorylation; Oxidoreductases; Rotenone; Spectrophotometry; Vitamin K

Topics: Animals; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Catalase; Drug Synergism; Glucose; Hydrogen Peroxide; Mice; Oxygen; Triazoles; Vitamin K

Topics: Animals; Body Temperature; Carcinoma, Ehrlich Tumor; Diethylstilbestrol; Fever; Glucose; Hot Temperature; Hydrogen-Ion Concentration; Mice; Oxygen; Partial Pressure; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Chromatography, Paper; Culture Techniques; Depression, Chemical; DNA, Neoplasm; Glucose; Hydrogen-Ion Concentration; Mice; Neoplasm Transplantation; Nucleic Acids; Nucleosides; Nucleotides; Oxygen; RNA, Neoplasm; Thymidine; Tritium; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Membrane; Diet Therapy; Dietary Fats; Fats, Unsaturated; In Vitro Techniques; Mice; Neoplasms, Experimental; Temperature; Vitamin K

Topics: Animals; Bone Marrow; Bone Marrow Cells; Bronchial Neoplasms; Carcinoma, Ehrlich Tumor; Chickens; Cricetinae; Culture Techniques; Digestive System; Disulfiram; Fibrosarcoma; Hot Temperature; Humans; Kidney; Lung; Mice; Myocardium; Neoplasms; Neoplasms, Experimental; Organ Specificity; Sarcoma, Experimental; Spleen; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Chromatography, Thin Layer; Fatty Acids, Essential; Glycolysis; Hot Temperature; Hydrogen Peroxide; In Vitro Techniques; Lipid Metabolism; Manometry; Mice; Peroxides; Vitamin K

Topics: Animals; Ascites; Body Temperature Regulation; Carcinoma, Ehrlich Tumor; Depression, Chemical; Diethylstilbestrol; Dimethyl Sulfoxide; Ethanol; Fever; Glucose; Mice; Rabbits; Stimulation, Chemical; Surface-Active Agents; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Dogs; Fatty Liver; Female; Fever; Hemorrhage; Male; Methylene Blue; Mice; Necrosis; Nephrosis; Rats; Sodium; Species Specificity; Sulfites; Vitamin K

Topics: Adenocarcinoma; Adult; Animals; Arsenicals; Carcinoma, Ehrlich Tumor; Carcinoma, Squamous Cell; Choriocarcinoma; DNA, Neoplasm; Female; Fluorides; Heparin; Humans; Lung Neoplasms; Lymphoma; Male; Malonates; Mandibular Neoplasms; Mice; Middle Aged; Neoplasms; Pregnancy; RNA, Neoplasm; Sarcoma; Testicular Neoplasms; Vitamin K

Topics: Animals; Carcinogens; Carcinoma, Ehrlich Tumor; Fever; Methylene Blue; Mice; Neoplasms; Trypan Blue; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Carcinoma, Krebs 2; Hot Temperature; Hydrogen Peroxide; In Vitro Techniques; Mice; Naphthoquinones; Oxygen; Partial Pressure; Spectrum Analysis; Sulfites; Trypan Blue; Vitamin K

Topics: Amobarbital; Animals; Arsenicals; Carcinoma, Ehrlich Tumor; Citrates; Enzyme Inhibitors; Fluorine; Fluoroacetates; Glucose; In Vitro Techniques; Mice; Mitochondria; Oxygen Consumption; Rotenone; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Catalase; Hot Temperature; Hydrogen Peroxide; Mice; Sodium; Sulfites; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Colorimetry; Humans; Injections, Intravenous; Mathematics; Rabbits; Sodium; Sulfites; Temperature; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; In Vitro Techniques; Naphthalenes; Radiation-Sensitizing Agents; Vitamin K

Topics: Aniline Compounds; Animals; Antimycin A; Ascorbic Acid; Carcinoma, Ehrlich Tumor; Cytochromes; Electron Transport; Hydroxybutyrates; In Vitro Techniques; Liver; Mitochondria; Oxidative Phosphorylation; Phenazines; Rats; Spectrophotometry; Succinates; Vitamin K

Topics: Animals; Ascites; Biochemical Phenomena; Biochemistry; Carcinoma; Carcinoma, Ehrlich Tumor; Mice; Neoplasms; Neoplasms, Experimental; Pharmacology; Radiation-Protective Agents; Radiation-Sensitizing Agents; Research; Sulfhydryl Compounds; Tritium; Vitamin K

Topics: Adrenochrome; Animals; beta-Aminoethyl Isothiourea; Carcinoma, Ehrlich Tumor; Radiation Injuries; Radiation Injuries, Experimental; Radiation-Protective Agents; Vitamin K

Topics: Animals; Carcinoma, Ehrlich Tumor; Diploidy; Neomycin; Retinoids; Vitamin K; Vitamin K 3

Topics: Adenosine Triphosphate; Animals; Ascites; Carcinoma; Carcinoma, Ehrlich Tumor; Diphosphates; Mice; Radiation-Sensitizing Agents; Vitamin K

Topics: Animals; Ascites; Carcinoma, Ehrlich Tumor; Diphosphates; Mice; Neoplasms, Experimental; Radiation-Sensitizing Agents; Vitamin K