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.

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.

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.

Quinapril for Sclerosis Failed in Long-Term Study

2007 ◽  
Vol 38 (6) ◽  
pp. 14
Author(s):  
DAMIAN MCNAMARA
Keyword(s):  
Term Study ◽  
Long Term Study
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