Selective toxicity of deoxyguanosine and arabinosyl guanine for T-leukemic cells.
Deoxyguanosine is selectively cytotoxic to leukemic cells from patients with T-acute lymphoblastic leukemia (T-ALL), whereas all other leukemic cell types were significantly less sensitive. Arabinosylguanine, a deoxyguanosine analog resistant to cleavage by purine nucleoside phosphorylase, is a more potent inhibitor of DNA synthesis in T-leukemic cells than deoxyguanosine and retains a selective cytotoxic activity for T-leukemic cells. Deoxyguanosine and arabinosylguanine are phosphorylated to deoxyGTP and arabinosylGTP, respectively, by T cells but not by other cell types. The phosphorylation and the cytotoxicity of arabinosylguanine are prevented by deoxycytidine. The selectivity of arabinosylguanine for malignant T cells, the exquisite sensitivity of these cells to the drug, and the failure of PNP to cleave the nucleoside indicate its potential in the treatment of T-ALL.
D001087:Arabinonucleosides / Q000633:toxicity*; D002478:Cells, Cultured; D003848:Deoxyguanine Nucleotides / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity*; D006147:Guanine / Q000096:biosynthesis; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D013601:T-Lymphocytes / Q000187:drug effects*
D001087:Arabinonucleosides; D003848:Deoxyguanine Nucleotides; C028771:9-arabinofuranosylguanine; D006147:Guanine; C029603:deoxyguanosine triphosphate; D003849:Deoxyguanosine