Metabolism of 1- β -d-Arabinofuranosylcytosine in Human Leukemic Cells

摘要: Summary The synthesis of nucleoside triphosphate (ara-CTP) from 1- β -d-arabinofuranosylcytosine (ara-C) in leukemic cells blood and bone marrow was measured vitro . Blood samples 74 patients 12 healthy donors were compared. During initial periods incubation (0 to 45 min), when ara-CTP linear, acute myelocytic or myelomonocytic leukemia patients, who currently previously sensitive ara-C therapy, produced twofold more than did chronic myelocytic, lymphocytic (acute chronic), normal subjects. In untreated particularly low levels may have negative prognostic value. All synthesized trapped intracellularly, and, at the level 15 ng/10 6 cells, inhibited incorporation [ methyl - 3 H]thymidine into DNA myeloblasts by 94%. Negligible amounts total radioactivity incorporated RNA during incubation. presence pyrimidine deaminase inhibitor, tetrahydrouridine (THU), leukemia, significantly increased. THU effect even prominent nonlinear phases (2 20 hr) which not only deamination but also partially blocked catabolic pathway ara-U. Samples relapsed showing secondary resistance, high ara-CTP; this result indicates that resistance is due factors other lack kinases phosphorylate ara-C. Thus, appear be a prerequisite, sufficient condition, for determining therapeutic efficacy present data suggest combined use with increase humans.