Ara-C incorporation into DNA.
نویسندگان
چکیده
منابع مشابه
A sensitive new method for clinically monitoring cytarabine concentrations at the DNA level in leukemic cells.
Cytarabine (ara-C), a major antileukemic agent, is phosphorylated in the cell to cytarabine triphosphate (ara-CTP), which is then partly incorporated into DNA. The drug incorporation into DNA poisons the extending primer against further incorporation of deoxyribonucleotides including dCTP, ultimately inhibiting DNA synthesis. While intracellular ara-CTP concentration has been found to predict c...
متن کاملRelationships among Ara-CTP pools, formation of (Ara-C)DNA, and cytotoxicity of human leukemic cells.
Cytosine arabinoside (Ara-C) is the most effective agent in the treatment of acute myelogenous leukemia. This agent incorporates in leukemic cell DNA, and the extent of this incorporation correlates with loss of clonogenic survival. The incorporated Ara-C residue behaves as a relative DNA chain terminator, and the extent of (Ara-C)DNA formation correlates with inhibition of DNA synthesis. The i...
متن کاملMetabolism of ara-C by blast cells from patients with ANLL.
The dose-response relationship between extracellular concentration of cytosine arabinoside (ara-C) and intracellular formation of the putative active metabolites of ara-C [ara-C incorporation into DNA and intracellular pools of ara-C in triphosphate form (ara-CTP)] was investigated in blast cells obtained from patients with acute nonlymphocytic leukemia (ANLL) by exposing these cells in vitro t...
متن کاملArabinosylguanine-induced apoptosis of T-lymphoblastic cells: incorporation into DNA is a necessary step.
9-Beta-D-Arabinosylguanine (ara-G) is a recently introduced and effective treatment for T-cell acute lymphoblastic leukemia, but how ara-G and ara-G triphosphate (ara-GTP) kill cells is not known. We hypothesized that, in cycling T-lymphoblastoid cells, ara-G may act directly by incorporation into DNA, which may lead to apoptosis. Hence, blocking the incorporation of ara-G monophosphate (ara-GM...
متن کاملDifferential incorporation of ara-C, gemcitabine, and fludarabine into replicating and repairing DNA in proliferating human leukemia cells.
The major actions of nucleoside analogs such as arabinosylcytosine (ara-C) and fludarabine occurs after their incorporation into DNA, during either replication or repair synthesis. The metabolic salvage and DNA incorporation of the normal nucleoside, deoxycytidine, is functionally compartmentalized toward repair synthesis in a process regulated by ribonucleotide reductase. The aim of this study...
متن کاملInfluence of fludarabine on pharmacokinetics and pharmacodynamics of cytarabine: implications for a continuous infusion schedule.
Arabinosylcytosine (ara-C) is a cytotoxic agent with major activity against acute leukemias. To exert this effect, it must first be phosphorylated to its active 5'-triphosphate, ara-CTP, which is incorporated into DNA. Our previous studies demonstrated that preincubation with arabinosyl-2-fluoroadenine (F-ara-A) increased the rate of ara-CTP accumulation in leukemia cells when incubated with 10...
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ورودعنوان ژورنال:
- Blood
دوره 65 1 شماره
صفحات -
تاریخ انتشار 1985