Purine metabolizing enzymes as predictors of lymphoblast sensitivity to deoxyadenosine

The toxicity of low concentrations of 2'-deoxyadenosine for T-lymphoblasts and certain null lymphoblasts has been attributed to the decreased degradation of the deoxynucleotides formed from deoxyadenosine in these cells. Low activities of the ectoenzymes ecto-5'-nucleotidase and ecto-ATPase have each been associated with deoxyadenosine sensitivity and dATP accumulation in human T-lymphoblasts. We studied a B-lymphoblast cell line, NC-37, which lacks detectable ecto-5'-nucleotidase and ecto-ATPase activities, but which is otherwise easily distinguishable from T-lymphoblasts by its low adenosine deaminase activity and its pattern of reactivity with monoclonal antibodies to cell surface antigens (Bl and IgM positive). The NC-37 B cells were completely analogous to other B-lymphoblast lines with high ectonucleotidase activities in their relative resistance to deoxyadenosine toxicity and low rates of dATP accumulation. This resistance could not be accounted for by lower rates of deoxyadenosine phosphorylating activity. Cytoplasmic nucleotidase activity in crude extracts from the NC-37 line was similar to that in other B-lymphoblasts with regard to both substrate specificity and optimal pH. We conclude that low ectonucleotidase activities are not etiologically associated with the accumulation of deoxynucleotides by human lymphoblasts, although they may serve as markers of deoxyadenosine sensitivity in certain malignant lymphoid cells.