Effects of cytosine arabinoside on human leukemia cells

Synthesis and evaluation of fatty acyl ester derivatives of cytarabine as anti-leukemia agents

“…The cytotoxic mechanism of cytarabine involves phosphorylation of 5 0 -hydroxyl into triphosphate, which on incorporation in nucleotide chain synthesis results into termination of chain elongation and thus inhibition of ribonucleotide synthesis and ultimately cell division inhibition [36]. The effectiveness of the cytarabine and cytarabine derivatives depends on the concentration of drug delivered intracellularly and availability of 5 0 -hydroxyl group.…”

Comparative effects of cycloguanil and WR99210 in human leukaemia cells and intra erythrocytic Plasmodium

“…The multidrug-resistant K1 strain of P. falciparum (Thaithong and Beale, 1981) was grown in erythrocytic culture (Yeo et al, 1997a). The effects of cycloguanil and WR99210 upon cellular levels of nucleotides (NTP and dNT P) were determ ined in leukaemia cells and P. falciparum grow ing in RPMI 1640 medium supplem ented with 10% (v/v) foetal calf serum (leukaem ia cells) or human serum (P. falciparum) (Seymour et al, 1994;Crisp et al, 1996). The concentrations of cycloguanil (2.5 m M) and WR99210 (1.0 m M) used were set several-fold above the upper limits of their physiological ranges to achieve maximal effects upon levels of NTP and dNTP within the 6-h exposure time to each drug.…”

“…The concentrations of cycloguanil (2.5 m M) and WR99210 (1.0 m M) used were set several-fold above the upper limits of their physiological ranges to achieve maximal effects upon levels of NTP and dNTP within the 6-h exposure time to each drug. Perchloric-acid extracts were prepared from leukaemia cells, and from parasites isolated after saponin lysis of erythrocytes, and NTP and dNTP in them were quanti® ed by high-performance liquid chrom atography (Crisp et al, 1996;Yeo et al, 1997a). The levels of nucleotides were calculated as attomol per leukaemia cell (amol/cell) or attomol per parasitised erythrocyte (amol/pe).…”

Association of genetic polymorphisms in genes involved in Ara-C and dNTP metabolism pathway with chemosensitivity and prognosis of adult acute myeloid leukemia (AML)

“…Intracellular Ara-C undergoes a three-step phosphorylation into the activate metabolite Ara-C triphosphate (ara-CTP) by deoxycytidine kinase ( DCK ) [ 8 ], cytidine monophosphate kinase 1 ( CMPK1 ) [ 9 ], and nucleoside diphosphate kinases (NDPKs) in turn [ 10 ]. Ara-CTP competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA, and thus results in blockade of DNA synthesis and cell death [ 11 ]. More recently, Schneider C and colleagues found that ara-CTP is hydrolyzed by the deoxynucleoside triphosphate (dNTP) triphosphohydrolase SAM domain and HD domain 1 ( SAMHD1 ), which promotes the detoxification of intracellular ara-CTP pools [ 12 ].…”