Ehrlich Ascites Tumor Cell Growth Research Articles

Effect of methotrexate on the intracellular phosphoribosyl pyrophosphate level and glucose transport of Ehrlich ascites tumor cells in vitro.

Methotrexate (MTX) suppressed the growth of Ehrlich ascites tumor (EAT) cells in vitro. The intracellular level of phosphoribosyl 5-pyrophosphate (PRPP) of EAT cells increased in a dose-dependent manner in response to MTX treatment. At the same time, the rate of glucose transport was lowered. Hypoxanthine reversed both these effects of MTX and partially rescued EAT cell growth. Under all conditions tested, changes in rate of glucose transport were shown to be the result of alterations in the number of glucose transporter (Vmax) rather than ligand affinity (Km). The dual action of MTX as a chemotherapeutic agent is discussed in this light.

Effects of creatine and β-guanidinopropionic acid on the growth of Ehrlich ascites tumor cells: i.p. injection and culture study

Growth of Ehrlich ascites tumor (EAT) cells in the abdominal space of mice or in cell culture was studied in response to i.p. injection or addition, respectively, of creatine or creatine analogue β-guanidinopropionic acid (β-GPA). The increase in body weight of the mice due to cancer growth was less in the β-GPA-injected than in the creatine- or sham-injected group. The volume of abdominal ascites and total cell counts at 11th day after implantation of EAT cells was significantly less in the β-GPA than in the other groups. The proliferation rate of EAT cells in the β-GPA group was 27% and 35% of the creatine- and sham-injected groups, respectively. Supplementation of creatine tended to enhance the growth of EAT cells. The creatine concentration in ascites fluid was approximately 4-times greater than in blood plasma of sham-injected control mice. But the creatine content in EAT cells was significantly reduced to approximately 50% in response to β-GPA injection. Cell culture without creatine caused a significant decrease in viability. The viability was improved, however, by addition of either creatine or serum into the medium. By contrast, it was not significantly increased by addition of serum alone which caused only a minor elevation of the creatine level (23 μM). It is suggested that EAT cell growth is inhibited by lowering the availability of creatine in association with some unknown factors in serum or ascites fluid.

Effect of Lactobacillus Acidophilus on Growth of Ehrlich Ascites Tumor in Swiss Mice

The role of Lactobacillus acidophilus LA 15 in reducing the proliferation of Ehrlich ascites tumor (EAT) was studied in Swiss male mice, over a period of 8 days. EAT cells were implanted intraperitoneally into mice on day 1 and the mice were subsequently treated intraperitoneally with whole cells of L. acidophilus. The mice were sacrificed on the eighth day to determine the effect of L. acidophilus on the proliferation of EAT cell growth. Control mice were injected with an equal volume of phosphate-buffered saline. There was a significant reduction in the proliferation of EAT cell due to L. acidophilus treatment. Three strains of L. acidophilus were efficacious in reducing the proliferation of EAT cell growth but the differences among L. acidophilus strains were not significant. Cell wall solids, but not non-cell wall solids reduced proliferation of EAT cells. Although L. acidophilus whole cells reduced proliferation of EAT cells, they were not as efficacious in decreasing proliferation of EAT cells in hy...

Feedback regulation of polyamine synthesis in Ehrlich ascites tumor cells. Analysis using nonmetabolizable derivatives of putrescine and spermine

Ornithine decarboxylase (ODC) is subject to feedback regulation by the polyamines. Thus, addition of putrescine, spermidine or spermine to cells causes inhibition of ODC mRNA translation. Putrescine and spermine are readily converted into spermidine. Therefore, it is conceivable that the inhibition of ODC synthesis observed in putrescine- and spermine-supplemented cells is instead an effect of spermidine. To examine this possibility we have used two analogs of putrescine and spermine, namely 1,4-dimethylputrescine and 5,8-dimethylspermine, which cannot be converted into spermidine. Both analogs were found to inhibit the incorporation of [35S]methionine into ODC protein to approximately the same extent, suggesting that putrescine as well as spermine exert a negative feedback control of ODC mRNA translation in the cell. In addition to suppressing ODC synthesis, both analogs were found to increase the turnover rate of the enzyme. 5,8-Dimethylspermine caused a marked decrease in the activity of S-adenosylmethionine decarboxylase (AdoMetDC). This effect was not obtained with 1,4-dimethylputrescine, indicating that spermine, but not putrescine, exerts a negative control of AdoMetDC. Treatment with 1,4-dimethylputrescine caused extensive depletion of the cellular putrescine and spermidine content, but accumulation of spermine. 5,8-Dimethylspermine treatment, on the other hand, effectively depleted the spermine content and had less effect on the putrescine and spermidine content, at least initially. Nevertheless, the total polyamine content was more extensively reduced by treatment with 5,8-dimethylspermine than with 1,4-dimethylputrescine. Accordingly, only 5,8-dimethylspermine treatment exerted a significant inhibitory effect on Ehrlich ascites tumor cell growth.

Feedback regulation of polyamine synthesis in Ehrlich ascites tumor cells. Analysis using nonmetabolizable derivatives of putrescine and spormine

Ornithine decarboxylase (ODC) is subject to feedback regulation by the polyamines. Thus, addition of putrescine, spermidine or spermine to cells causes inhibition of ODC mRNA translation. Putrescine and spermine are readily converted into spermidine. Therefore, it is conceivable that the inhibition of ODC synthesis observed in putrescine- and spermine-supplemented cells is instead an effect of spermidine. To examine this possibility we have used two analogs of putrescine and spermine, namely 1,4-dimethylputrescine and 5,8-dimethylspermine, which cannot be converted into spermidine. Both analogs were found to inhibit the incorporation of [ 35S]methionine into ODC protein to approximately the same extent, suggesting that putrescine as well as spermine exert a negative feedback control of ODC mRNA translation in the cell. In addition to suppressing ODC synthesis, both analogs were found to increase the turnover rate of the enzyme. 5,8-Dimethylspermine caused a marked decrease in the activity of S-adenosylmethionine decarboxylase (AdoMetDC). This effect was not obtained with 1,4-dimethylputrescine, indicating that spermine, but not putrescien, exerts a negative control of AdoMetDC. Treatment with 1,4-dimethylputrescine caused extensive depletion of the cellular putrescine and spermidine content, but accumulation of spermine. 5,8-Dimethylspermine treatment, on the other hand, effectively depleted the spermine content and had less effect on the putrescine and spermidine content, at least initially. Nevertheless, the total polyamine content was more extensively reduced by treatment with 5,8-dimethylspermine than with 1,4-dimethylputrescine. Accordingly, only 5,8-dimethylspermine treatment exerted a significant inhibitory effect on Ehrlich ascites tumor cell growth.

Irreversible inhibition of the early increase in ornithine decarboxylase activity following growth stimulation is required to block Ehrlich ascites tumor cell proliferation in culture

Summary Ehrlich ascites tumor cell growth in culture was inhibited by α-difluoromethylornithine, an enzyme-activated irreversible inhibitor of ornithine decarboxylase, provided that treatment was initiated at the time of growth stimulation. When α-difluoromethylornithine was added after the activation of polyamine synthesis caused by the growth stimulus, i.e. when a 3–5-fold increase in putrescine and spermidine content had occurred, cell proliferation was completely unaffected. α-Methylornithine, a competitive inhibitor of ornithine decarboxylase, did not affect cell proliferation even when added at the time of growth stimulation. Compared to α-difluoromethylornithine, α-methylornithine only produced a partial and transient decrease in the cellular putrescine and spermidine content.

Inhibition of purine biosynthesis de novo and of Ehrlich ascites tumor cell growth by 6-methylmercaptopurine ribonucleoside

Inhibition of purine biosynthesis de novo and of Ehrlich ascites tumor cell growth by 6-methylmercaptopurine ribonucleoside

Isolation of naturally occurring inhibitors of ribonucleotide reductase

Ribonucleotide reductase activity was markedly inhibited by components isolated from Ehrlich ascites cells. These components were much more inhibitory to ribonucleotide reductase than to DNA polymerase from these cells. 14C-Thymidine incorporation studies showed that in general, there was a correlation between the degree of inhibition of reductase activity and the degree of inhibition of 14C-Thymidine incorporation into DNA of intact cells. Preliminary studies showed that this inhibitory fraction was also capable of retarding Ehrlich ascites tumor cell growth in mice.