Phosphorylation of Adenosine and Deoxyadenosine in Ehrlich Ascites Carcinoma Cells Resistant to 6-(Methylmercapto)purine Ribonucleoside

Abstract

The metabolism of adenosine and deoxyadenosine has been studied in Ehrlich ascites tumor cells and in a subline (EAC-R2) resistant to growth inhibition by 6-(methylmercapto)purine ribonucleoside (6MeMPR). The mutant cell line showed reduced rates of conversion of adenosine and deoxyadenosine into nucleotides. It was concluded from this that both compounds probably are phosphorylated by adenosine kinase. Comparison of the rates of nucleotide synthesis at increasing concentrations of adenosine indicated differences in the Km and Vmax values of the adenosine kinases in the parent and mutant strains. Competition experiments between adenosine and 6MeMPR showed that adenosine kinase in EAC-R2 had probably lost all affinity for the analogue. Selection for resistance to 6MeMPR therefore seems to have altered the structure of adenosine kinase, such that it has no activity with 6MeMPR and reduced activity with adenosine and deoxyadenosine.