Consequences of the salvage of purine compounds on the proliferation of rat T-lymphocytes with normal or inhibited purine de novo synthesis.
We studied the ability of purine compounds to restore the proliferation of concanavalin-A-stimulated rat T-lymphocytes under conditions of purine de novo synthesis inhibition and, on the other hand, the inhibition by purine nucleosides of the response of these cells to a mitogenic stimulation under conditions of normal purine de novo synthesis. The use of 50 microM azaserine, a potent inhibitor of purine de novo synthesis, allowed us to define the physiologically active salvage pathways of purine bases, ribo- and deoxyribonucleosides in concanavalin-A-stimulated rat T-lymphocytes. Except for guanylic compounds, all purines completely restored cell proliferation at a concentration of 50 microM. Guanine, guanosine and 2'-deoxyguanosine at concentrations up to 500 microM did not allow us to restore more than 50% of the cell proliferation. In conditions of normal purine de novo synthesis, the addition of 1000 microM adenine, adenosine, 2'-deoxyadenosine or 100 microM 2'-deoxyguanosine inhibited rat T-lymphocyte proliferation. The differences between the degree of inhibition of cell proliferation could be explained only in part by the differences between the capacities of salvage of these compounds. Furthermore, the fact that 2'-deoxyguanosine toxicity was dependent and 2'-deoxyadenosine toxicity independent on the activation state of the cells provided more evidence that the biochemical mechanisms of inhibition of cell proliferation should be different for these two nucleosides.
D000659:AMP Deaminase / Q000037:antagonists & inhibitors; D058892:Adenosine Deaminase Inhibitors; D000818:Animals; D001377:Azaserine / Q000494:pharmacology; D003208:Concanavalin A / Q000494:pharmacology; D003839:Deoxyadenosines / Q000494:pharmacology; D003849:Deoxyguanosine / Q000494:pharmacology; D005260:Female; D006148:Guanine Deaminase / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors; D011687:Purines / Q000096:biosynthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013601:T-Lymphocytes / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D011687:Purines; D003208:Concanavalin A; D001377:Azaserine; D011683:Purine-Nucleoside Phosphorylase; D006148:Guanine Deaminase; D000659:AMP Deaminase; D003849:Deoxyguanosine; D013936:Thymidine