linoleic-acid and Carcinoma--Ehrlich-Tumor

Electric field pulses used for cell manipulation can cause irreversible cell damage. The mechanisms of the processes leading to such cell damage are very complicated. Our work demonstrated that exponential electric pulses with intensity of 2-7.5 kV/cm and duration of 5.2 ms were able to initiate peroxidation of fatty acid emulsions, liposomal membranes, red blood and Ehrlich ascite tumor cells. Electric pulses-induced peroxidation of erythrocyte membranes was followed by hemolysis. The electric treatment caused damage of E. coli membrane lipids which was accompanied by decreased cell survival. All these effects depended on field intensity. A relatively good correlation between pulse-induced peroxidation of erythrocyte membranes and hemolysis was observed. These results suggest that free radical mediated processes as lipid peroxidation and/or lipid degradation or fragmentation may be possible causes for electric pulses-induced irreversible cell damage.

Topics: Animals; Carcinoma, Ehrlich Tumor; Electroporation; Emulsions; Erythrocyte Membrane; Escherichia coli; Free Radical Scavengers; Hemolysis; In Vitro Techniques; Kinetics; Linoleic Acid; Linoleic Acids; Lipid Peroxidation; Liposomes; Membrane Lipids; Membranes, Artificial; Mice; Oxidation-Reduction; Rats; Thiobarbituric Acid Reactive Substances; Tumor Cells, Cultured

We investigated the effects of oleic acid and linoleic acid on transplanted Ehrlich ascites carcinoma and Ehrlich solid carcinoma in ACR mice. Both acids significantly prolonged the life spans of Ehrlich ascites carcinoma-bearing mice and inhibited the growth of Ehrlich solid carcinoma in mice compared with the findings in untreated control mice. Methyl esters of these acids also prolonged the survival of Ehrlich ascites carcinoma-bearing mice, but they were less effective in lengthening the survival of mice given transplants of Ehrlich ascites carcinoma. In addition, gas-chromatography analysis of tumor cell lipids showed that appreciable changes occurred in the fatty acid composition of the tumor cell grown in mice treated with oleic acid or linoleic acid. Linoleic acid caused more pronounced alterations in fatty acid composition of tumor cell lipids than did oleic acid, a feature that parallels the intensity of the cytotoxicity potential of the two free fatty acids. These results suggest that (a) the free carboxyl group of free fatty acids plays a role in killing tumor cells and (b) the modification of the fatty acid composition of tumor cells also correlates with the antitumor effects of oleic and linoleic acids. In addition, these results indicate that free fatty acids may be of tumor-oriented distribution; as a consequence, free fatty acids selectively inhibit the growth of tumor cells.

Topics: Animals; Carboxylic Acids; Carcinoma, Ehrlich Tumor; Cell Division; Esters; Fatty Acids; Fatty Acids, Nonesterified; Linoleic Acid; Linoleic Acids; Male; Mice; Mice, Inbred Strains; Neoplasm Transplantation; Oleic Acid; Oleic Acids

Wide attention has been given to hyperthermia as a new measure for cancer treatment. Clinical trials of hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic we examine if fatty acids exert a synergistic effect on Ehrlich ascites tumour cells when combined with hyperthermia, as they possess antitumour activity on some occasions. When cells were incubated with oleic acid and linoleic acid (unsaturated fatty acids) at 37 degrees C, the DNA synthesis of cells was significantly inhibited. Palmitic and stearic acids, which are saturated fatty acids, did not suppress DNA synthesis. Hyperthermic treatment without the presence of fatty acids at 42 degrees C for 1 h decreased DNA synthesis to 62% of the control level of 37 degrees C. The combination of an unsaturated fatty acid and hyperthermia synergistically suppressed DNA synthesis. When the cells were incubated in serum-free medium containing 0.1% albumin, unsaturated fatty acids were more effective in inhibiting DNA synthesis. However, saturated fatty acids had little or no effect on DNA synthesis in control or hyperthermia-treated cells. These results indicate that unsaturated fatty acids are useful for enhancing the inhibitory effect of hyperthermia on DNA synthesis, which may increase the in vitro antitumour effects of hyperthermia.

Topics: Animals; Carcinoma, Ehrlich Tumor; Culture Media; DNA, Neoplasm; Fatty Acids, Unsaturated; Female; Hot Temperature; Linoleic Acid; Linoleic Acids; Mice; Oleic Acid; Oleic Acids; Palmitic Acids; Stearic Acids; Tumor Cells, Cultured

Mixed micelles (MM) composed of polyoxyethylated (60 mol) hydrogenated castor oil (HCO60) as a harmless surfactant and linoleic acid (LA) as an essential fatty acid potentiated the antitumor activity of bleomycin (BLM). In the in vivo experiment, intraperitoneal administration of BLM with MM significantly prolonged the survival time of male ddY mice bearing Ehrlich ascites tumor and male Donryu rats bearing ascites hepatoma AH 66 inoculated intraperitoneally, compared with that of animals treated with BLM alone, BLM with HCO60, and BLM with LA, respectively, whereas MM had no antitumor effect to both tumors. Also in Winn-type tumor-neutralizing assay in which 10 male ddY mice were innoculated intraperitoneally with Ehrlich ascites tumor cells preincubated with a test material, BLM with MM showed a more marked enhancing activity with 3 surviving tumor-free mice than did BLM alone.

Topics: Animals; Bleomycin; Carcinoma, Ehrlich Tumor; Castor Oil; Colloids; Drug Synergism; Linoleic Acid; Linoleic Acids; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred Strains; Micelles; Rats; Rats, Inbred Strains; Surface-Active Agents

We tried to understand why our earlier estimates of fatty acid (FA) oxidation rates under the nearly anaerobic state of the Ehrlich ascites tumor (EAT) in vivo were even greater than those found in vitro under aerobic conditions. Using tracers [1-14C]linoleate, [1-14C]-, and [9,10-3H]palmitate, and NaH14CO3, we estimated essential and nonessential FA oxidation rates to CO2 + H2O by EAT in living mice and in vitro under aerobic and anaerobic conditions. Sequestration of intraperitoneally (ip)-injected 14C-FFA allowed a selective labeling of the tumor versus the host; thus, breath 14CO2 could be used to estimate the maximum rate of FA oxidation in vivo by the tumor. Initially, we measured breath 14CO2 following NaH14CO3 injections and developed a multicompartmental model to simulate the tumor-host HCO-3-CO2 system. This model was integrated with our earlier model for tumor FA turnover. The integrated model was fitted to breath 14CO2 data from mice injected ip with 14C-FFA to compute tumor FA oxidation rates. Both essential and nonessential FA were oxidized to CO2 at similar rates. The maximum rate of total FA oxidation to CO2 was 5-6 nmol FA X min-1 X 7-ml tumor-1, about 5-10 times lower than all previous estimates obtained in vitro and in vivo. To resolve this dilemma we used doubly labeled [1-14C; 9,10-3H]palmitate and found that under aerobic conditions, in vitro, EAT formed 3H2O and 14CO2 at nearly equal rates. These rates were suppressed markedly but unequally at low PO2. Anaerobic suppression of 14CO2 formation greatly exceeded that of 3H2O formation. As a result 3H2O/14CO2 reached a value of congruent to 10 at low PO2. Our data indicate that under the nearly anaerobic conditions of a growing EAT in vivo, the partial beta-oxidation of FA to 2C + H2O takes place at a 5 to 10 times faster rate than the complete oxidation of FA to CO2 + H2O. This finding can account for earlier apparent inconsistencies in the literature, since aerobic studies of 14C-FA oxidation to 14CO2 in vitro and of 3H-FA oxidation to 3H2O under nearly anaerobic conditions would both overestimate greatly the rate of FA oxidation to CO2 by EAT in vivo.

Topics: Animals; Bicarbonates; Body Water; Carbon Dioxide; Carcinoma, Ehrlich Tumor; False Positive Reactions; Fatty Acids, Nonesterified; In Vitro Techniques; Linoleic Acid; Linoleic Acids; Male; Mice; Models, Biological; Oxidation-Reduction; Oxygen; Palmitic Acid; Palmitic Acids; Sodium Bicarbonate

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Membrane; Fatty Acids, Unsaturated; Linoleic Acid; Oleic Acid; Oleic Acids; Research; Ribosomes

Topics: Animals; Ascites; Biochemical Phenomena; Carbohydrate Metabolism; Carbohydrates; Carcinoma, Ehrlich Tumor; Linoleic Acid; Lipid Metabolism; Neoplasms