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One of the models used for studying cancer is the Ehrlich ascites tumor (EAT) due to its ability to grow in liquid suspension, allowing a standard number of cells to be inoculated, growth quantification and regression of tumor mass. Among the oncostatic substances, melatonin has shown effectiveness in limiting the tumor cell proliferation. However, studies have shown contradictory effects of melatonin on the EAT. This study has investigated the melatonin effect on tumor growth, time and survival percentage, ultrastructure and metastasis of EAT cells in mice submitted or not to pinealectomy.

Graphical abstractDisplay Omitted Highlights� Oscillabolastic model used to capture oscillatory dynamics. � Relevance of oscillatory dynamics to biology systems described. � Hes1 gene expression accurately described using the oscillabolastic model. � Generalized model proposed to accommodate multivariate cases. This paper introduces a new dynamical model, called the oscillabolastic model, to analyze the dynamical behavior of biomedical data when one observes oscillatory behavior. The proposed oscillabolastic model is sufficiently flexible to represent various types of oscillatory behavior. The oscillabolastic model is applied to two sets of data. The first data set deals with the oscillabolastic modeling of Ehrlich ascites tumor cells and the second one is the oscillabolastic modeling of the mean signal intensity of Hes1 gene expression in response to serum stimulation. A generalized oscillabolastic model is also suggested to accommodate cases in which predictor variables other than time are also involved.

In a previous study, we showed that (1′S)-acetoxychavicol acetate ((S)-ACA) caused a rapid decrease in glutathione (GSH) levels less than 15 min after exposure. (S)-ACA-induced cell death was reversed by the addition of N-acetylcysteine. In the current study, we investigated the inhibitory activities of 13 derivatives of (S)-ACA on tumor cell viability, intracellular GSH level and GR activity. Correlations were found among a decrease in cell viability, intracellular GSH levels and the activity of GR in Ehrlich ascites tumor cells treated with the various ACA analogues. A test of the 13 derivatives revealed that the structural factors regulating activity were as follows: (1) the para or 1′-position of acetoxyl group (or other acyl group) was essential, (2) the presence of a C2′–C3′ double or triple bond was essential, and (3) the S configuration of the 1′-acetoxyl group was preferable.

Roots of Decalepis hamiltonii are consumed as pickles and as a beverage and are believed to possess health-promoting properties. Roots of D. hamiltonii exhibit antioxidant properties. We have isolated an antioxidant compound from the aqueous extract of the roots of D. hamiltonii and identified it as ellagic acid (EA), based on NMR and MS. EA exhibited free radical-scavenging activity, inhibited LDL oxidation and showed cytoprotective effect against xenobiotic-induced oxidative stress in Ehrlich Ascites tumor cells. EA is a new addition to the list of antioxidant compounds in the roots of D. hamiltonii.

In the present work, we studied the effects of two titanocenes, biscyclopentadienyldichlorotitanium IV, (DDCT) and its derivative, biscyclopentadienylditiocianatetitanium IV (BCDT), on the activity of natural killer (NK) cells in Ehrlich ascites tumour (EAT)-bearing BALB/c mice. In order to investigate a more direct effect of these compounds on NK cell function, we performed experiments with severe combined immunodeficiency (SCID) mice, which exhibit a normal NK cell response in the absence of T and B cells. The treatment consisted of intraperitoneal (i.p.) administration of 15 mg/kg/day of DDCT for 2 days or 10 mg/kg/day of BCDT for 3 days. In addition, to verify whether the effects produced by the titanocenes were compound specific or related to a direct antitumour effect, we also investigated the effects of a 3-day treatment with 100 mg/kg of cyclophosphamide cyclophosphamide on NK cell activity. Our results demonstrated that, in BALB/c and SCID mice, NK cell function declined to subnormal levels after inoculation of the tumour. In these animals, although treatment with DDCT and BCDT significantly enhanced NK cell function, only DDCT restored NK cell activity to normal values in all stages studied. Conversely, treatment with cyclophosphamide reduced NK cell function in nontumour bearing SCID mice and was also unable to restore the decreased NK activity of tumour-bearing SCID mice, thus demonstrating that the enhancement of NK cell function by titanocenes is compound specific. The same effect of cyclophosphamide was observed with BALB/c mice. In the present study, the up-modulatory effects of these two compounds on NK cell function reveal a new aspect of the mechanism of antitumoural action of titanocenes.

Rhein has been shown to inhibit the uptake of glucose into Ehrlich Ascites tumor cells. In this paper we show that a wide range of antrhaquinones related to rhein can also inhibit glucose uptake into chondrocytes, many significantly more than the parent molecule.

We determined the effect of 13 days of treatment with 2.0 mg/kg haloperidol (s.c) on the development of the Ehrlich solid carcinoma, after inoculation of 1.5 x 10(6) Ehrlich ascites tumor cells into the left footpad of mice. The footpad thickness of haloperidol treated animals was significantly smaller than control from day two after tumor inoculation, to the end of the experiment. Histopathological examination showed that haloperidol treated mice apparently presented less necrotic areas within the tumor mass as well as less invasion of subepithelial connective tissue and other adjacent structures. In particular, in comparison with the control group, no nerve bundles were invaded by neoplastic cells in experimental mice. The possible mechanism underlying these results is discussed in light of the specific pharmacological properties of this neuroleptics drug.

The presence of calcyclin in the microsomal fraction of Ehrlich ascites tumor cells was detected using polyclonal antibodies. Association of calcyclin with the microsomes depended on the presence of calcium ions in the buffer used for cell fractionation. The interaction of calcyclin with Ehrlich ascites tumor cells microsomes was confirmed in the in vitro conditions by cosedimentation assay using exogenous calcyclin. It was shown that phospholipids extracted from natural membranes and purified phosphatydylserine or phosphatydylcholine were not involved in the binding. Instead, several low molecular weight polypeptides in the Triton X-100 resistant membrane fraction were found to interact with calcyclin.

Native plasma membrane fractions isolated from Ehrlich ascites tumor cells were used as the starting point for two easy and efficient procedures to functionally reconstitute ferricyanide reductase activity. The obtained proteoliposomes showed high specific activities. The reconstituted ferricyanide reductase seemed to have one or more cysteine essential residues, as judged by inhibition with sulfhydryl reagents.

1. 1. Three calcium-binding proteins have been purified from Ehrlich ascites tumor cells. 2. 2. They were identified by amino acid sequence analysis on selected fragments obtained by tryptic digestion. 3. 3. The proteins belong to the annexin family and were identified as annexins II, III and V. 4. 4. Antibodies raised against the proteins were used to examine for their presence in a number of murine tissues. 5. 5. The occurrence was found to be in reasonable accordance with earlier reports.

Exposure of Ehrlich ascites tumor (EAT) cells to the anticancer drug cisplatin results in an elevated abundance of three isoforms of the small heat shock protein hsp25 without inducing the general stress response as commonly observed after heat shock. The most effective cisplatin concentration (2.5 microM) is also most efficient in arresting cells in S phase suggesting a relationship between hsp25 expression and cell cycle events. Exposure to cisplatin results also in an increased thermotolerance of EAT cells.

Ehrlich ascites tumour cells (EAT-F5) were irradiated in vitro with the sparsely ionizing “plateau pions” and with the more densely ionizing “peak pions”. From cell survival curves obtained under euoxic and hypoxic conditions, the RBE for the production of irreparable lethal and potentially lethal damage was derived. Cells of the same strain were used to produce solid tumours in the leg muscle of mice. Survival of these cells irradiated in vivo was compared with the corresponding in vitro data. It can be concluded that a large fraction of hypoxic cells is present in these tumours and that repair takes place in vivo at least as much as under the in vitro conditions. These solid tumours were irradiated with 5 dose fractions of fast protons as reference radiation, and the probability p T of tumour destruction was determined as a function of dose. Irradiation with a spot of “plateau pions” indicated the same p T as a function of dose, but side effects in the intestinal tract increased also with dose, leading to the death of the animals. The probability for avoiding these side effects in the animals, p S , was also determined. Using both values, p T and p S , the probability for local tumour control was estimated. Irradiation with “peak pions” resulted in an RBE of about 2.5 for tumour destruction corresponding to the RBE found in vitro for the production of irreparable lethal lesions in hypoxic cells. Side effects in the mouse gut showed a RBE of 2.0, corresponding to irreparable lethal lesions in euoxic in vitro cells.

A slight but significant short-term incoporation (15 and 60 min) of glucose-carbon into DNA and RNA was detected in Ehrlich ascites tumour cells incubated in the presence of labelled glucose (5 mM). Glutamine (0.5 mM) increased the incorporation of glucose but did not modify the glycolytic flux.

The effect of i.p. injected epirubicin-free or entrapped in gelatin microspheres with or without calcium channel inhibitor (nifedipine) on the development of Ehrlich ascites in mice was studied. The experiments were carried out on 409 Swiss mice. All animals were i.p. grafted with 1.5 × 106 tumor cells and divided into six groups: gr. I control; gr. II i.p. free epirubicin; gr. III i.p. epirubicin loaded microspheres; gr. IV i.p. free epirubicin + nifedipine; gr. V i.p. epirubicin loaded microspheres + nifedipine; gr. VI i.p. nifedipine. Our results show statistically significant differences of the survival time between groups I, VI and groups II, III, IV, V. The less toxic effects were observed in groups treated with epirubicin loaded microspheres (UI and V). Our results demonstrate that epirubicin loaded microspheres alone or associated with nifedipine, improve the survival time and decrease the toxicity of the drug.

Crude alcoholic extracts of zoanthids, indigenous to Hawaii, have been shown to have general antitumor activity against Ehrlich ascites tumor in mice. The toxic component, palytoxin, was effective in the control and cure of Ehrlich ascites at extremely low dosages using several different methods of administration and displayed marginal activity against P-388 lymphocytic leukemia.

An indirect exposure of mice during their fetal stage of development to Ehrlich ascites tumor cells alters the animals' response to this tumor during their adult life. Control mice injected intraperitoneally with Ehrlich tumor cells react in various ways to the presence of this alien tissue. The response is expecially evident during the first 48–72 h post-injection. Several aspects of this complex reaction are absent in those animals which were exposed to this tumor in utero. The measurably altered reactivity toward the Ehrlich tumor cells is hereditary. Possible mechanisms of this alteration are discussed.

Hyperacetylated chromatin was isolated from Ehrlich ascites tumor cells grown in n -butyrate containing medium and fractionated by mild digestion with deoxyribonuclease II and precipitation with MgCl 2 . The most highly acetylated forms of histones H4 and H3 as well as the acetylated subspecies of H2B were found almost entirely associated with the putatively active Mg 2+ -soluble chromatin fraction. The Mg 2+ -insoluble fraction contained mainly mono- and diacetylated molecules of H4 and H3.

Changes in the electrophoretic mobility of mammalian cells following irradiation with X, δ and β rays are reported. The cells investigated were human and cockerel erythrocytes and Ehrlich Ascites Tumour Cells. The electrophoretic mobility of the cells showed a biphasic response with dose. The general trend of the response was that the cockerel erythrocytes showed an initial increase in mobility, then a return to normal levels. Human erythrocytes and ascites cells exhibited an initial decrease in mobility before returning to the control values. The X and δ dose levels required for these changes were similar and substantially greater than when β radiations were used.

DNA from Ehrlich ascites tumor cells incubated with [3 H]thymidine was analyzed for the fraction of radioactive label adsorbed to nitrocellulose at higher ionic strengths. The exact progress of label incorporation within time was recorded for pulse and pulse-chase experiments. The dependence of the label fraction binding to nitrocellulose on the particle size of the DNA samples examined supported the hypothesis that the growing point itself causes the nitrocellulose affinity of nascent DNA. A simplified mathematical model based on this hypothesis yielded expectation values fitting the experimental data obtained with DNA pulse-labeled for 1 min assuming a growth rate of 1.5 μm/min. The binding label fraction of pulse-chase labeled DNA (1 min–1 h) was considerably higher than the corresponding expectation values. The possible significance of these results in respect to the existence of distinct units of replication (replicons) in the mammalian cell genome is discussed.

Neutral gossypol solution injected peritoneally into NMRI mice preimplanted with Ehrlich ascites tumour cell, at a dose of 25-100 micrograms/mouse per day, lengthened the number of survival days of the hosts. This gossypol effect on tumour cell proliferation is concentration dependent. The optimum dose is 100 micrograms. However, at too high a dose, the gossypol caused a body weight loss and the death of the tumour-bearing mice.

With the whole set of the tested anthracyclines, a bimodal localization, nuclear and lysosomal, is observed. But the percentage of the drug which is stored in the nuclei is different according to the drug. With some derivatives which have a high therapeutic efficiency, 82–87 % of the drug is recovered in the nuclei. In a second group whatever the biological activity of the drug only 49–52 % of the drug accumulates in the nuclei.

(3H)poly(ADP-ribose) synthesized from nuclei by incubation with (3H)NAD was released from protein by alkaline treatment and electrophoresed in dodecyl sulfate gels. Individual polymers up to at least 33 units were completely separated according to their chain length. Size distribution was visualized by fluorography of the gels, and quantified by radioactivity determination of sliced gels The method could be applied to crude nuclear extracts. It showed that nuclei of Ehrlich ascites tumor cells produced a poly(ADP-ribose) pattern distinctly different from that of rat liver nuclei.

Male swiss mice were implanted with Ehrlich ascites tumor cells and fed ad libitum either yogurt or yogurt components. Ad libitum feeding of yogurt for 7 consecutive days after tumor implantation significantly (P

Summary The effect of anaerobiosis and oxygen recovery on the DNA synthesis of Ehrlich ascites cells was studied by alkaline sucrose gradient centrifugation after pulse labeling the daughter chain DNA of operating replication units by [ 3 H]-thymidine. Removal of oxygen from cells growing in culture caused a strong inhibition of initiation of new units. When oxygen was resupplied initiation reappeared subsequently. The kinetics of restoration of a normal length distribution of the daughter chains of operating units indicated that the initiation pattern in the reaerated cells was normal.

Mouse Kupffer cells prelabelled with carbon or iron migrate to the necrotic centrilobular zone by 48 h following CCl 4 -induced necrosis. Thereafter the cells remain asociated with the shrinking necrotic zone. Total healing of the liver injury is not accompanied by total loss of the labelled Kupffer cells. Repopulation of the liver by new phagocytic cells from the circulation follows closely on the migration. Evidence is presented to indicate that unlabelled Kupffer cells also migrate. The existence of an undefined Kupffer cell-mobilizing factor, and local centrilobular chemotactic forces, are postulated to explain the observed phenomena.

uptake and glycolysis in this rapidly proliferating tumor. In the current study, we have concentrated more on the mechanistic than on the physiological aspects of the carrier, its charge specificity, charge and pH transfer behavior, cation dependence, and covalent inhibitors.

A new method is described for the purification of the intermediate filament protein vimentin from Ehrlich ascites tumor cells using single-stranded DNA-cellulose affinity chromatography. The procedure is rapid and allows the large scale isolation of the protein. Partial characterization of vimentin shows that it has a molecular weight of 58000 and an apparent pI of 5.3. It can be degraded by the vimentin-specific, Ca 2+ -activated proteinase which results in the production of a characteristic set of degradation products. The vimentin also cross-reacts with the intermediate filament protein monoclonal antibody, α-IFA.

Four titanocene derivatives containing hydrophilic ligands were tested for antiproliferative activity against Ehrlich ascites tumor in mice. The new compounds (C 5 H 5 ) 2 TiCl( p -SC 6 H 4 NH 3 + Cl − ) ( I ) and (C 5 H 5 ) 2 Ti( p -SC 6 H 4 NH 3 + Cl − ) 2 ( II ), containing hydrochlorinated p -aminothiophenolate ligands, and the known compounds (C 5 H 5 ) 2 Ti( cis -OOCCHCHCOOH) 2 ( III ) and (C 5 H 5 ) 2 Ti(OOCCCl 3 ) 2 ( IV ) containing the carboxylic acid anions hydrogen- maleinate and trichloroacetate as acido ligands, induced maximum cure rates of 100%. The T.I. values amounted to 4.4–4.6 ( I ), 3.5–4.1 ( II ), 3.7– 3.8 ( III ) and 5.5 ( IV ), and were slightly increased in comparison to (C 5 H 5 ) 2 TiCl 2 (T.I. = 3.3). The complexes I – III were rather soluble in water and equally active in a DMSO/saline (1/9, v/v) mixture, in pure saline and in buffered solutions. In the case of IV , the toxicity was considerably low (LD 50 ,440 mg/kg; LD 100 , 500 mg/kg) in relation to (C 5 H 5 ) 2 TiCl 2 (LD 50 , 100 mg/kg; LD 100 , 140 mg/kg).

Incubation of Ehrlich ascites cells with normal or C1q or C2 deficient human sera results in killing of the cells. Killing occurred also in the absence of free Ca++, which supported by the fact that factor B and C3 were cleaved, leads to the conclusion that the alternative pathway of the complement system is activated on the surface of the Ehrlich ascites cells.

Encephalomyocarditis virus infection of mouse Ehrlich ascites tumour or L-cells or human HeLa cells inhibits the activation of the ppp(A2′p)n A-dependent nuclease and prevents the binding of a radioactive analogue of ppp(A2′p)n A to the ppp(A2′p)n A binding protein. This loss or inactivation of the ppp(A2′p)n A-dependent nuclease in response to virus infection is prevented by interferon pretreatment of the cells.

Two forms of native 40 S ribosomal subunits, distinguishable by their buoyant densities, are recovered from Ehrlich ascites cells. In this communication, we describe experiments designed to test whether Met-tRNAf is associated with either form. Our results indicate that (a) in the cell, Met-tRNAf is bound to the native 40 S subunit, and in particular, to the subunit of density 1.40 g x cm-3; (b) under the growth conditions used, less than 10% of the low density native subunits have bound Met-tRNAf; (c) the majority of the Met-tRNAf containing native 40 S subunits, isolated from sucrose gradient analyses of cell extracts, join with 60 S subunits in vitro to form 80 S monosomes only if additional ribosomal wash factors are provided; and (d) the 80 S monosomes so formed are completed initiation complexes that can form peptide bonds. These results support the hypothesis that various forms of the native 40 S subunit represent different stages in the formation of a complete initiation complex.

The fluorescence intensity of the cynanine dye DiO-C 6 -(3)_in 0.32% suspension of Ehrlich ascites tumor cells was determined under various potassium concentrations. In addition, the fluorescence levels of cell-free buffer solutions and those of supernatants were measured. For every potassium concentration the partition of the dye between cells and medium was calculated and its relation to the potassium gradient was given. A model was developed which assumes the fluorescence of a cell suspension to be the sum of the fluorescence signal of dye in the extracellular medium and that of cell-associated dye. A calibration curve of fluorescence vs. membrane potential was constructed. Neither the fluorescence of the cell suspension nor that of the supernatants was a linear function of the membrane potential. The limitations of membrane potential determination by fluorimetric methods are discussed.

Resume Le flux a travers la pyruvate deshydrogenase a ete dose sur les cellules tumorales d'ascite d'Ehrlich par le 14CO2 forme a partir du pyruvate [114C]. Des incubations paralleles ont ete realisees dans un milieu avec CO2 (25 mM NaCO3H) et dans un milieu sans bicarbonate. L'activation du complexe enzymatique par les ions NH+4 a ete observee seulement dans le milieu bicarbonate, parce que la dilution isotopique du CO2 dans ce milieu permet la recuperation du 14CO2 forme par la decarboxylation de l'acide pyruvique. Dans un milieu sans bicarbonate, l'activation du complexe enzymatique n'a pas ete observee, car le 14CO2 forme dans les cellules est consomme par des reactions biosynthetiques. Au contraire, dans les cellules hepatiques isolees, l'activation par les ions NH+4 est observee quand les ions NH+4 sont presents dans les deux milieux. Comme cela a ete decrit pour d'autres tissus de mammiferes l'activite de la pyruvate deshydrogenase est inversement proportionnelle au rapport ATP/ADP dans la mitochondrie.

The ability of Ehrlich ascites tumour (EAT) cells in mice to take up glucose as well as the density of glucose carriers on the cells increased progressively during the course of tumour development. Simultaneously as the rate of uptake rose, the intracellular phosphoribosyl diphosphate (PRPP) levels dropped responding to the decrease of serum glucose. Hyperglycaemia induced in the host by alloxan or streptozotocin administration increased the serum glucose concentrations and intracellular PRPP levels but decreased the density of glucose carriers of the cells, whereas insulin administration reversed this condition. The physiological significance of these observations are discussed.

1. 1. The small molecular weight RNA components C, A, K and L isolated from nuclei of Ehrlich ascites cells and baby hamster kidney cells are homogeneous when analyzed on different types of polyacrylamide gels at neutral and acid pH with or without high concentrations of urea. 2. 2. Component D consists of two components.

Resume La fonction des cycles du phospho-3-glycerate et du malate-aspartate, pendant la glycolyse, a ete etudiee par des approches experimentales differentes sur deux souches de cellules tumorales d'ascite d'Ehrlich. Les enzymes qui catalysent ces cycles ont ete dosees dans le milieu cytosolique et dans le milieu mitochondrial apres fractionnement des cellules, prealablement permeabilisees par la digitonine. On peut conclure que le cycle du phospho-3-glycerate ne fonctionne pas, faute d'enzymes et par absence de stimulation de la respiration par le glucose en presence de rotenone. L'analyse des niveaux des metabolites intermediaires de la glycolyse en presence d'aminoxyacetate indique que la fonction du cycle du malate-aspartate est tres faible. Le bilan du glucose consomme et de l'acide lactique produit, suggere l'existence d'une autre voie d'oxydation du NADH cytosolique, qui depend de l'acetyl-CoA. Le dosage des enzymes citrate synthase, ATP citrate lyase et malicodeshydrogenase, suggere que le cycle du malate-citrate est fonctionnel.

Ehrlich ascites cell microsomes catalyze the exchange of the acyl group of acyl dihydroxyacetone phosphate with free fatty acids. The reaction does not require ATP and CoA.