THE ENZYMIC FORMATION OF 6-(METHYLMERCAPTO)PURINE RIBONUCLEOSIDE 5′-PHOSPHATE

1966 ◽  
Vol 44 (2) ◽  
pp. 229-245 ◽  
Author(s):  
Ian C. Caldwell ◽  
J. Frank Henderson ◽  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Blood Cells ◽  
Intraperitoneal Injection ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Ehrlich Ascites ◽  
Mouse Tissues ◽  
Enzymatic Methods

6-(Methylmercapto)purine ribonucleoside (Me6MPR) is efficiently phosphorylated in mouse tissues and in Ehrlich ascites carcinoma cells in vivo; tumor cells in vitro and cell-free extracts of the tumor also phosphorylate this analogue ribonucleoside. The product of this reaction has been identified by chemical and enzymatic methods and by its chromatographic behaviour as Me6MPR 5′-phosphate. The evidence presented in this report indicates that no other major metabolites of Me6MPR are formed.The phosphorylation of Me6MPR by cell-free tumor extracts requires ATP and Mn2+ (or Mg2+), and evidence is presented that the reaction is probably mediated by adenosine kinase.Me-14C-6MPR is rapidly taken up by most mouse tissues following its intraperitoneal injection. Forty minutes after injection of the labeled drug, the highest levels of radioactivity were found in intestine, liver, blood cells, lung, and spleen, in descending order; virtually no radioactivity was found in brain tissue or in blood plasma.

THE ROLE OF THIOL GROUPS IN THE DEVELOPMENT OF RADIATION DAMAGE IN THYMOCYTES AND EHRLICH ASCITES CARCINOMA CELLS

1964 ◽  
Vol 42 (12) ◽  
pp. 1717-1727 ◽  
Author(s):  
J. F. Scaife
Keyword(s):  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Irradiation Damage ◽  
Thiol Groups ◽  
Protein Thiol ◽  
Ehrlich Ascites ◽  
X Irradiation ◽  
The Difference

The effect of 800–1000 rads of X-irradiation on the thiol content of thymocytes and Ehrlich ascites carcinoma cells has been compared. Four hours after irradiation there was a decrease in the non-protein thiol (NP.SH) content of thymus and thymocytes but no change in ascites cells. In both cells the main NP.SH compound was glutathione. There was no significant effect of irradiation on the protein thiol (P.SH) content of thymus or ascites cells, but there was a slight decrease in P.SH in thymocytes after 4 hours incubation. Isolated thymus nuclei showed an immediate small decrease in P.SH content following 800 rads in vitro. Nuclei isolated from rat thymus 1 hour after 1000 rads in vivo showed an increase in the SH content of the globulin fraction and a decrease in the SH content of the nucleohistones. The total SH content of thymocytes and ascites cells was reduced by slow diffusion of H2O2into the cell suspension, but no effect of prior irradiation on this decrease of SH was found. Inhibition of catalase in vivo and in vitro did not produce any of the morphological signs of irradiation damage in thymocytes. There was no effect of irradiation on the copper content of thymus, thymocytes, or ascites cells. The ratio of NP.SH/P.SH is higher in thymocytes than in ascites cells, but, allowing for the difference in cell size, the overall total thiol concentration was the same. Anoxia produced only a small increase in NP.SH content in both cells and a small and doubtful increase in P.SH. It is concluded that, if thiol groups are involved in cell sensitivity to radiation, only a small fraction of the total SH groups are involved at critical sites.

THE SYNTHESIS OF EXTRACELLULAR RIBONUCLEOSIDES BY ASCITES TUMOR CELLS IN VITRO

1965 ◽  
Vol 43 (2) ◽  
pp. 257-269 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Ascites Tumor ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells

Ehrlich ascites carcinoma cells in vitro converted extracellular hypoxanthine to extracellular inosine if uridine or guanosine was provided in the medium at the rate of 20–30 μmoles per milliliter of cells per hour. The synthesis of external uridine also took place when cells were incubated with uracil and a purine ribonucleoside, but at a lower rate than that of inosine. Intact Ehrlich ascites cells catalyzed an exchange between labelled uracil and uridine when both were present in the incubation medium.The synthesis of the extracellular ribonucleoside appeared to be mediated by ribonucleoside phosphorylases and to take place by the transfer of the ribosyl group from a donor ribonucleoside to an acceptor base.

THE FORMATION OF 6-MERCAPTOPURINE RIBOSIDE PHOSPHATE IN ASCITES TUMOR CELLS

1959 ◽  
Vol 37 (8) ◽  
pp. 1011-1023 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Solid Tumor ◽  
Carcinoma Cells ◽  
Sarcoma 180 ◽  
Ascites Tumor ◽  
Enzymatic Methods

A nucleotide metabolite of 6-mercaptopurine has been isolated from Erhlich ascites carcinoma cells exposed to this compound under in vivo and in vitro conditions. By chemical and enzymatic methods, this nucleotide has been identified as 6-mercaptopurine nucleoside-5′-monophosphate.6-Mercaptopurine nucleotide is formed rapidly in the tumor cells in vivo, maximum concentrations being achieved within 0.5 hours after administration of the analogue. Treatment of the tumor cells with 6-mercaptopurine or with azaserine induced a twofold to threefold enhancement in their ability to synthesize 6-mercaptopurine nucleotide.Using isotopic techniques small amounts of 6-mercaptopurine nucleotide were detected in liver, intestine, and a solid tumor. The conversion of 6-mercaptopurine to the nucleotide form was also demonstrated in an ascitic form of Sarcoma 180.

INHIBITION OF RIBONUCLEOSIDE METABOLISM IN EHRLICH ASCITES TUMOR CELLS BY PURINE ANALOGUE RIBONUCLEOSIDES

1965 ◽  
Vol 43 (10) ◽  
pp. 1701-1710 ◽  
Author(s):  
A. R. P. Paterson ◽  
A. I. Simpson
Keyword(s):  
Tumor Cells ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Ehrlich Ascites Tumor Cells ◽  
Purine Analogues ◽  
Intact Cells ◽  
Ehrlich Ascites ◽  
Derivatives Of ◽  
Related Compounds

Several aspects of the metabolism of inosine and uridine by Ehrlich ascites carcinoma cells in vitro have been found to be inhibited by ribonucleoside derivatives of four purine analogues. The synthesis of both inosine and uridine by intact tumor cells was profoundly inhibited in the presence of 6-methylmercaptopurine ribonucleoside. Also inhibited were inosine and uridine cleavage, and the exchange of isotope between these ribonucleosides and the corresponding C14 labelled bases. These reactions, however, were not inhibited when they took place in broken-cell preparations. Similarly, inosine metabolism in intact cells (but not in broken cells) was profoundly inhibited by three related compounds: the ribonucleosides of the 6-chloro, 6-methylmercapto, and 6-propylmercapto derivatives of 2-aminopurine.

THE FORMATION OF 6-MERCAPTOPURINE RIBOSIDE PHOSPHATE IN ASCITES TUMOR CELLS

1959 ◽  
Vol 37 (1) ◽  
pp. 1011-1023 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Solid Tumor ◽  
Carcinoma Cells ◽  
Sarcoma 180 ◽  
Ascites Tumor ◽  
Enzymatic Methods

A nucleotide metabolite of 6-mercaptopurine has been isolated from Erhlich ascites carcinoma cells exposed to this compound under in vivo and in vitro conditions. By chemical and enzymatic methods, this nucleotide has been identified as 6-mercaptopurine nucleoside-5′-monophosphate.6-Mercaptopurine nucleotide is formed rapidly in the tumor cells in vivo, maximum concentrations being achieved within 0.5 hours after administration of the analogue. Treatment of the tumor cells with 6-mercaptopurine or with azaserine induced a twofold to threefold enhancement in their ability to synthesize 6-mercaptopurine nucleotide.Using isotopic techniques small amounts of 6-mercaptopurine nucleotide were detected in liver, intestine, and a solid tumor. The conversion of 6-mercaptopurine to the nucleotide form was also demonstrated in an ascitic form of Sarcoma 180.

Trichosanthes dioica seed lectin inhibits Ehrlich ascites carcinoma cells growth in vivo in mice by inducing G 0 /G 1 cell cycle arrest

2021 ◽  
Author(s):  
Shaikh Shohidul Islam ◽  
Md. Rezaul Karim ◽  
A. K. M. Asaduzzaman ◽  
A. H. M. Khurshid Alam ◽  
Zahid Hayat Mahmud ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Cycle Arrest ◽  
Ehrlich Ascites ◽  
Trichosanthes Dioica
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