THIOPURINE NUCLEOTIDE SYNTHESIS IN A 6-MP-RESISTANT SUBLINE OF THE EHRLICH ASCITES CARCINOMA AND GROWTH INHIBITION BY CERTAIN ANTIMETABOLITES

1960 ◽  
Vol 38 (10) ◽  
pp. 1129-1135 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Growth Inhibition ◽  
Tumor Cells ◽  
Test Dose ◽  
Ehrlich Ascites Carcinoma ◽  
Tumor Line ◽  
Nucleotide Synthesis ◽  
Parent Line ◽  
Ehrlich Ascites ◽  
Ascites Tumors ◽  
Hydrolysis Of

A 6-MP-resistant subline of the Ehrlich ascites carcinoma has been characterized as cross-resistant to thioguanine and is more sensitive to azaserine than the parent tumor line. The resistant subline has retained the sensitivity to amethopterin shown by the parent tumor line. 6-MP riboside was no more effective than 6-MP in inhibiting the growth of the resistant cells.It was shown previously that cells of this resistant subline, in contrast to cells of the parent line, were unable to synthesize 6-MP nucleotide from a test dose of 6-MP injected into the ascitic fluid. In the present study it was shown that resistant cells were also unable to convert 6-MP riboside or thioguanine to their nucleotide derivatives, both of which were synthesized by the 6-MP-sensitive parent line of tumor cells. Similarities observed in the metabolism of 6-MP and 6-MP riboside and in their chemotherapeutic effects were probably due to the extensive hydrolysis of 6-MP riboside which took place in both ascites tumors.

THIOPURINE NUCLEOTIDE SYNTHESIS IN A 6-MP-RESISTANT SUBLINE OF THE EHRLICH ASCITES CARCINOMA AND GROWTH INHIBITION BY CERTAIN ANTIMETABOLITES

1960 ◽  
Vol 38 (1) ◽  
pp. 1129-1135
Author(s):  
A. R. P. Paterson
Keyword(s):  
Growth Inhibition ◽  
Tumor Cells ◽  
Test Dose ◽  
Ehrlich Ascites Carcinoma ◽  
Tumor Line ◽  
Nucleotide Synthesis ◽  
Parent Line ◽  
Ehrlich Ascites ◽  
Ascites Tumors ◽  
Hydrolysis Of

A 6-MP-resistant subline of the Ehrlich ascites carcinoma has been characterized as cross-resistant to thioguanine and is more sensitive to azaserine than the parent tumor line. The resistant subline has retained the sensitivity to amethopterin shown by the parent tumor line. 6-MP riboside was no more effective than 6-MP in inhibiting the growth of the resistant cells.It was shown previously that cells of this resistant subline, in contrast to cells of the parent line, were unable to synthesize 6-MP nucleotide from a test dose of 6-MP injected into the ascitic fluid. In the present study it was shown that resistant cells were also unable to convert 6-MP riboside or thioguanine to their nucleotide derivatives, both of which were synthesized by the 6-MP-sensitive parent line of tumor cells. Similarities observed in the metabolism of 6-MP and 6-MP riboside and in their chemotherapeutic effects were probably due to the extensive hydrolysis of 6-MP riboside which took place in both ascites tumors.

THE DEVELOPMENT OF RESISTANCE TO 6-MERCAPTOPURINE IN A SUBLINE OF THE EHRLICH ASCITES CARCINOMA

1960 ◽  
Vol 38 (10) ◽  
pp. 1117-1127 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Ehrlich Ascites Carcinoma ◽  
Term Study ◽  
Tumor Line ◽  
Parent Line ◽  
Development Of Resistance ◽  
Long Term Study ◽  
Ehrlich Ascites

A subline of the Ehrlich ascites carcinoma has been developed which grows under 6-mercaptopurine (6-MP) therapy at approximately five times the rate of the parent line. Cells of the resistant subline were almost completely incapable of converting 6-MP to 6-MP nucleotide in contrast to those of the parent tumor line. A relationship between resistance to 6-MP and the capacity of the tumor cells to synthesize 6-MP nucleotide was indicated by a long-term study of these properties in branches of the resistant tumor subline which were maintained with and without exposure to 6-MP.

THE DEVELOPMENT OF RESISTANCE TO 6-MERCAPTOPURINE IN A SUBLINE OF THE EHRLICH ASCITES CARCINOMA

1960 ◽  
Vol 38 (1) ◽  
pp. 1117-1127 ◽  
Author(s):  
A. R. P. Paterson
Keyword(s):  
Tumor Cells ◽  
Ehrlich Ascites Carcinoma ◽  
Term Study ◽  
Tumor Line ◽  
Parent Line ◽  
Development Of Resistance ◽  
Long Term Study ◽  
Ehrlich Ascites

A subline of the Ehrlich ascites carcinoma has been developed which grows under 6-mercaptopurine (6-MP) therapy at approximately five times the rate of the parent line. Cells of the resistant subline were almost completely incapable of converting 6-MP to 6-MP nucleotide in contrast to those of the parent tumor line. A relationship between resistance to 6-MP and the capacity of the tumor cells to synthesize 6-MP nucleotide was indicated by a long-term study of these properties in branches of the resistant tumor subline which were maintained with and without exposure to 6-MP.

Die Wirkung von 9.10-Phenanthrenhydrochinon-bisglycylester auf den Ehrlich-Ascites-Tumor der Maus und das Jensen-Sarkom der Ratte

1963 ◽  
Vol 18 (12) ◽  
pp. 1053-1056 ◽  
Author(s):  
U. Dold ◽  
H. J. Risse ◽  
H. Tiedemann
Keyword(s):  
Enzymatic Hydrolysis ◽  
Ehrlich Ascites Carcinoma ◽  
Carcinoma Cells ◽  
Redox Cycle ◽  
Ascites Tumor ◽  
Low Oxygen ◽  
Ehrlich Ascites ◽  
Ehrlich Ascites Cells ◽  
Ascites Tumors ◽  
Hydrolysis Of

9.10-phenanthrahydroquinone formed by the enzymatic hydrolysis of 9.10-phenanthrahydroquinone-bisglycylester undergoes a redox-cycle in tumor-cells. H2O2 is formed during the autoxidation of the hydroquinone. The amount of H2O2 is especially large in aerobically glycolyzing cells.The cancerostatic action of the hydroquinone-bisglycylester was tested on Ehrlich-Ascites-carcinoma-cells and on Jensen-sarcoma. When Ehrlich-Ascites-cells preincubated with 3.4 to 8.4·10-5 Mol/l Ester for 30 minutes at 37°C are injected into mice, the development of Ascites-tumors is inhibited. Injection of the ester directly into Ascites-tumors has no effect. One of the reasons for this may be the low oxygen content of the Ascites-tumor, which does not permit the redox-cycle to operate.In a part of the cases full regression of Jensen-sarcoma was obtained after injecting 8.2·10-5 Mol/kg Ester 2 - 3 times intravenously every of 2 -3 days.

Effects of Bikaverin on purine nucleotide synthesis and catabolism in ehrlich ascites tumor cells in vitro

1977 ◽  
Vol 26 (21) ◽  
pp. 1973-1977 ◽  
Author(s):  
J.Frank Henderson ◽  
Mary L. Battell ◽  
George Zombor ◽  
Jan Fuska ◽  
P. Nemec
Keyword(s):  
Tumor Cells ◽  
Ehrlich Ascites Tumor ◽  
Purine Nucleotide ◽  
Ehrlich Ascites Tumor Cells ◽  
Ascites Tumor ◽  
Nucleotide Synthesis ◽  
Ehrlich Ascites

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.

Further Investigations on the p-Nitrophenylphosphatase Activity of Intact Ehrlich Ascites Tumor Cells

1978 ◽  
Vol 33 (3-4) ◽  
pp. 227-230 ◽  
Author(s):  
Reiner Merz ◽  
Monika Löffler ◽  
Friedhelm Schneider
Keyword(s):  
Tumor Cells ◽  
Active Sites ◽  
Ehrlich Ascites Tumor ◽  
Ehrlich Ascites Tumor Cells ◽  
Ascites Tumor ◽  
Intact Cells ◽  
Blocking Agents ◽  
Ehrlich Ascites ◽  
Eat Cells ◽  
Hydrolysis Of

The substrate specificity and the effects of nucleotides and SH-blocking agents on the p-nitro- phenylphosphatase activity of intact Ehrlich ascites tumor cells (EAT) cells were studied, ᴅʟ-β- Glycerophosphate, o-phosphoethanolamine, cholinephosphate, glucose-6-phosphate, o-carboxyphenyl- phosphate,, phosphoenolpyruvate and AMP were not attacked by intact cells. ATP > GTP > UTP > PPi > pNPP were cleaved with decreasing velocity. A stimulation of the cleavage of p-NPP by the following nucleotides was observed with decreasing effectivity: ATP > ADP > GTP > UTP; AMP was ineffective. The phosphatase activity was not affected by malate, tartrate and glutathion disulfide. The SH blocking agents diamide and thimerosal were more effective in­hibitors of the pNPPase than of the ATPase activity, whereas the hydrolysis of ATP is more affected by the ATP analog adenylylimidodiphosphate. The present data are best compatible with a double headed enzyme: Both active sites interact with ATP, only one is active against p-NPP and sensitive against SH-blocking agents.

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